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Biomarker Predictors of Clinical Efficacy of the Anti-IgE Biologic Omalizumab in Severe Asthma in Adults: Results of the SoMOSA Study.

Background: The anti-IgE monoclonal antibody omalizumab is widely used for severe asthma. This study aimed to identify biomarkers that predict clinical improvement during 1 year of omalizumab treatment. Methods: One-year open-label Study of Mechanisms of action of Omalizumab in Severe Asthma (SoMOSA) involving 216 patients with severe (Global Initiative for Asthma step 4/5) uncontrolled atopic asthma (at least two severe exacerbations in the previous year) taking high-dose inhaled corticosteroids and long-acting β-agonists with or without maintenance oral corticosteroids. It had two phases: 0-16 weeks, to assess early clinical improvement by Global Evaluation of Therapeutic Effectiveness (GETE); and 16-52 weeks, to assess late responses based on ⩾50% reduction in exacerbations or mOCS dose. All participants provided samples (exhaled breath, blood, sputum, urine) before and after 16 weeks of omalizumab treatment. Measurements and Main Results: A total of 191 patients completed phase 1; 63% had early improvement. Of 173 who completed phase 2, 69% had reduced exacerbations by ⩾50% and 57% (37 of 65) taking mOCSs had reduced their dose by ⩾50%. The primary outcomes 2,3-dinor-11-β-PGF2α, GETE score, and standard clinical biomarkers (blood and sputum eosinophils, exhaled nitric oxide, serum IgE) did not predict either clinical response. Five volatile organic compounds and five plasma lipid biomarkers strongly predicted the ⩾50% reduction in exacerbations (receiver operating characteristic areas under the curve of 0.780 and 0.922, respectively) and early responses (areas under the curve of 0.835 and 0.949, respectively). In an independent cohort, gas chromatography/mass spectrometry biomarkers differentiated between severe and mild asthma. Conclusions: This is the first discovery of omics biomarkers that predict improvement in asthma with biologic agent treatment. Prospective validation and development for clinical use is justified.

Mechano-pharmacology of T cell receptor specificity.

Unlocking the potential of electronic blood transfusion systems: Implementation insights from NHS hospitals in England.

Electronic blood transfusion (EBT) systems have the potential to significantly enhance patient safety and healthcare efficiency. Although national guidelines recommend their implementation, widespread adoption requires addressing gaps in evidence regarding cost-effectiveness and clinical impact. This study assessed EBT implementation in English hospitals via a 2023 survey focusing on three key components: (i) electronic blood fridges (EBFs) for traceability and stock management, (ii) electronic blood ordering systems with clinical decision support (CDSS) and (iii) bedside patient identification (PID) systems. The survey also examined EBT integration with electronic health records (EHRs) and inter-hospital record linkages. Among 206 surveyed hospitals, 114 responded, resulting in a 55.6% response rate. Of the responding sites, 76 (67.3%) had implemented at least one EBT component. EBFs were the most adopted technology (65 sites; 57.5%), followed by bedside identification systems (37 sites; 32.7%). Advanced systems like CDSS were implemented in only 16 sites (14.2%). Barriers to adoption included financial constraints, limited senior management engagement and technical challenges. Our results show variability in EBT system adoption across NHS England hospitals. There is a pressing need for cost-effectiveness analyses to support investment decisions, while evidence of clinical effectiveness is needed to justify advanced EBT systems and overcome organisational barriers.

Randomised controlled trial of a behaviour change physiotherapy intervention to increase physical activity following hip and knee replacement: the PEP-TALK trial.

OBJECTIVE: To test the effectiveness of a behaviour change physiotherapy intervention to increase physical activity compared with usual rehabilitation after total hip replacement (THR) or total knee replacement (TKR). DESIGN: Multicentre, pragmatic, two-arm, open, randomised controlled, superiority trial. SETTING: National Health Service providers in nine English hospitals. PARTICIPANTS: 224 individuals aged ≥18 years, undergoing a primary THR or TKR deemed 'moderately inactive' or 'inactive'. INTERVENTION: Participants received either six, 30 min, weekly, group-based exercise sessions (usual care) or the same six weekly, group-based, exercise sessions each preceded by a 30 min cognitive behaviour discussion group aimed at challenging barriers to physical inactivity following surgery (experimental). RANDOMISATION AND BLINDING: Initial 75 participants were randomised 1:1 before changing the allocation ratio to 2:1 (experimental:usual care). Allocation was based on minimisation, stratifying on comorbidities, operation type and hospital. There was no blinding. MAIN OUTCOME MEASURES: Primary: University of California Los Angeles (UCLA) Activity Score at 12 months. Secondary: 6 and 12-month assessed function, pain, self-efficacy, kinesiophobia, psychological distress and quality of life. RESULTS: Of the 1254 participants assessed for eligibility, 224 were included (139 experimental: 85 usual care). Mean age was 68.4 years (SD: 8.7), 63% were women, 52% underwent TKR. There was no between-group difference in UCLA score (mean difference: -0.03 (95% CI -0.52 to 0.45, p=0.89)). There were no differences observed in any of the secondary outcomes at 6 or 12 months. There were no important adverse events in either group. The COVID-19 pandemic contributed to the reduced intended sample size (target 260) and reduced intervention compliance. CONCLUSIONS: There is no evidence to suggest attending usual care physiotherapy sessions plus a group-based behaviour change intervention differs to attending usual care physiotherapy alone. As the trial could not reach its intended sample size, nor a proportion of participants receive their intended rehabilitation, this should be interpreted with caution. TRIAL REGISTRATION NUMBER: ISRCTN29770908.

Getting Recovery Right After Neck Dissection (GRRAND-F): Mixed-methods feasibility study to design a pragmatic randomised controlled trial.

OBJECTIVE: To determine the feasibility of a randomised controlled trial to estimate the effectiveness and cost-effectiveness of a rehabilitation intervention following neck dissection (ND) after head and neck cancer (HNC). DESIGN: Two-arm, open, pragmatic, parallel, multicentre, randomised controlled feasibility trial. SETTING: Two UK NHS hospitals. PARTICIPANTS: People who had HNC in whom a ND was part of their care. We excluded those with a life expectancy of six months or less, pre-existing, long-term neurological disease affecting the shoulder and cognitive impairment. INTERVENTION: Usual care (standard care supplemented with a booklet on postoperative self-management) was received by all participants. The GRRAND intervention programme consisted of usual care plus up to six individual physiotherapy sessions including neck and shoulder range of motion and progressive resistance exercises, advice and education. Between sessions, participants were advised to complete a home exercise programme. RANDOMISATION: 1:1 randomisation. Allocation was based on minimisation, stratified by hospital site and spinal accessory nerve sacrifice. It was not possible to mask treatment received. MAIN OUTCOME MEASURES: Primary: Participant recruitment, retention and fidelity to the study protocol and interventions from study participants and staff at six months post-randomisation (and 12 months for those reaching that time-point). Secondary: clinical measures of pain, function, physical performance, health-related quality of life, health utilisation and adverse events. RESULTS: 36 participants were recruited and enrolled. The study achieved five of its six feasibility targets. These included consent - 70% of eligible participants were consented; intervention fidelity - 78% participants discharged completed the intervention sessions; contamination - none - no participants in the control arm received the GRRAND-F intervention and retention - 8% of participants were lost to follow-up. The only feasibility target that was not achieved was the recruitment target where only 36 of the planned 60 participants were recruited over 18 months. This was principally due to the COVID-19 pandemic which caused all research activity to be paused or reduced, with a subsequent reduction in. CONCLUSIONS: Based on the findings a full-trial can now be designed to better understand whether this proposed intervention is effective. CLINICAL TRIAL REGISTRATION: https://www.isrctn.com/ISRCTN1197999, identifier ISRCTN11979997.

Head and Neck Cancer: United Kingdom National Multidisciplinary Guidelines, Sixth Edition.

Cognitive behavioral therapy for eating disorders: A map of the systematic review evidence base.

OBJECTIVE: To map and examine the systematic review evidence base regarding the effects of cognitive-behavioral therapy (CBT) for eating disorders (EDs), especially against active interventions. METHOD: This systematic review is an extension of an overview of CBT for all health conditions (CBT-O). We identified ED-related systematic reviews from the CBT-O database and performed updated searches of EMBASE, MEDLINE, and PsychInfo in April 2021 and September 2022. RESULTS: The 44 systematic reviews included (21 meta-analyses) were of varying quality. They focused on "high intensity" CBT, delivered face-to-face by qualified clinicians, in BN, BED and mixed, not specifically low-weight samples. ED-specific outcomes were studied most, with little consensus on their operationalization. The, often insufficient, reporting of sample characteristics did not allow assessment of the generalizability of findings. The meta-analytic syntheses show that high intensity one-to-one CBT produces better short-term effects than a mix of active controls especially on ED-specific measures for BED, BN, and transdiagnostic samples. There is little evidence favoring group CBT or low intensity CBT against other active interventions. DISCUSSION: While this study found evidence consistent with current ED treatment recommendations, it highlighted notable gaps that need to be addressed. There were insufficient data to allow generalizations regarding sex and gender, age, culture and comorbidity and to support CBT in AN samples. The evidence for group CBT and low intensity CBT against active controls is limited, as it is for the longer-term effects of CBT. Our findings identify areas for future innovation and research within CBT. PUBLIC SIGNIFICANCE: This study provides a comprehensive mapping and quality assessment of the current large systematic review research base regarding the effects of cognitive behavioral therapy (CBT) for eating disorders (EDs), with a focus on comparisons to other active interventions. By transcending the more limited scope of individual systematic reviews, this overview highlights the gaps in the current evidence base, and thus provides guidance for future research and clinical innovation.

SWAT 110: Printing the primary outcomE on Pink PapER versus standard paper to increase participant engagement to postal questionnaires (PEPPER)

Background: Missing data is a common issue in randomised controlled trials. There is a need to rigorously test means of participant retention. This embedded trial aims to examine the effect on postal response rates of printing a randomised controlled trial’s primary outcome on pink versus white paper. Methods: Our randomised Study Within A Trial (SWAT) was run within a behaviour-change intervention host trial for patients following hip or knee replacements. Participants were randomised to receive the host trial’s primary outcome measure printed on either a sheet of pink or white paper within the 11 sheet (21 page) six-month follow-up questionnaire. The SWAT’s primary outcome was host trial primary outcome measure completion. Number of reminders sent, proportion of remaining questions completed and overall questionnaire returns were secondary outcomes. Results: 176 participants were randomised: 88 received pink paper, 88 white paper. Host trial primary outcome measures were returned by 84.1% (74/88 participants) in the pink paper group and in 90.9% (80/88 participants) in the white paper group (risk ratio, 0.92 [95% CI 0.80, 1.06]; p=0.24). Reminders were sent to 48.9% (43/88 participants) in the pink paper group and in 30.7% (27/88 participants) in the white paper group (risk ratio 1.59 [95% CI 1.09, 2.33]; p=0.01). No other results were statistically significant. Conclusion: Printing the primary outcome on pink paper does not increase data return. From this small randomised study, there is some evidence that it potentially decreases response and is more burdensome to collect postal data by increasing the necessity for reminders.

Treatments for enhancing sleep quality in fibromyalgia: a systematic review and meta-analysis.

OBJECTIVES: Sleep disturbance is a key symptom of fibromyalgia and a risk factor for chronic widespread pain. This systematic review and meta-analysis aims to assess the effectiveness of pharmacological treatments and cognitive behavioural therapy (CBT) in improving sleep quality in fibromyalgia patients. METHODS: A systematic search of PubMed, MEDLINE, Embase, Cochrane CENTRAL, and CINAHL was conducted for randomized controlled trials (RCTs) published up to April 2023. Studies assessing pharmacological or CBT interventions with sleep-related outcomes were included. Data were extracted, and meta-analyses were performed where applicable. Study quality and bias were evaluated using the Cochrane Risk of Bias tool. RESULTS: Forty-seven RCTs, including 11094 participants, were reviewed. CBT for insomnia (CBT-I) showed a significant improvement in sleep quality (SMD -0.63, 95%CI -0.98 to -0.27), while CBT for pain (CBT-P) had no significant impact. Pharmacological agents such as pregabalin and sodium oxybate moderately improved sleep, but there was uncertainty around this evidence. Amitriptyline, milnacipran, and duloxetine showed no significant benefit for sleep. Study heterogeneity was moderate, and no publication bias was detected. CONCLUSION: CBT-I is a promising treatment for enhancing sleep quality in fibromyalgia. Pharmacological treatments like pregabalin may be beneficial but should be used cautiously due to potential risks. Future research should prioritise trials focusing on sleep as a primary outcome and explore the comparative effectiveness of pharmacological treatments and CBT-I in fibromyalgia. Understanding the mechanisms linking sleep and fibromyalgia will also help guide future therapies.

Clinical effectiveness of an individually tailored strengthening programme, including progressive resistance exercises and advice, compared to usual care for ambulant adolescents with spastic cerebral palsy (ROBUST trial): a parallel group randomized controlled trial.

AIMS: Muscle strengthening exercises are one of the interventions frequently prescribed by physiotherapists for adolescents with cerebral palsy (CP). However, there is wide variability in the exercise regimes used and limited evidence of their effectiveness. The ROBUST trial will assess the clinical effectiveness of an individually tailored strengthening programme, including progressive resistance exercises and advice, compared to usual care for ambulant adolescents with spastic CP. METHODS: We are conducting a multicentre, two-arm, parallel group, superiority randomized controlled trial. We will recruit adolescents aged 12 to 18 years with a diagnosis of spastic CP (bilateral or unilateral) Gross Motor Function Classification System (GMFCS) levels I to III who are able to comply with the assessment procedures and exercise programme with or without support. Participants will be recruited from at least 12 UK NHS Trust physiotherapy and related services. Participants (n = 334) will be randomized (centralized computer-generated 1:1 allocation ratio) to either: 1) a progressive resistance exercise programme, with six one-to-one physiotherapy sessions over 16 weeks; or 2) usual NHS care, with a single physiotherapy session and an assessment session, and advice regarding self-management and exercise. CONCLUSION: The primary outcome is functional mobility measured using the child-/parent-reported Gait Outcomes Assessment List (GOAL) at six months. Secondary outcomes are: clinician-assessed muscle strength (Five Times Sit-to-Stand Test) and motor function (timed up and go test) at six months; functional mobility (GOAL) at 12 months; independence (GOAL subdomain A), balance (GOAL subdomain A, B, D), pain and discomfort (GOAL subdomain C), health-related quality of life (youth version of the EuroQol five-dimension questionnaire; EQ-5D-Y), educational attendance, exercise adherence, and additional physiotherapy treatment (six and 12 months). The primary analysis will be intention to treat.

Clinical effectiveness of a child-specific dynamic stretching programme, compared to usual care, for ambulant children with spastic cerebral palsy (SPELL trial): a parallel group randomized controlled trial.

AIMS: Dynamic muscle stretching exercises are one of the interventions frequently prescribed by physiotherapists for children with cerebral palsy (CP). However, there is wide variability in the exercise regimes used and limited evidence of their effectiveness. The SPELL trial will assess the clinical effectiveness of an individually tailored dynamic stretching programme, compared to usual care for ambulant children with spastic CP. METHODS: We are conducting a multicentre, two-arm, parallel group, superiority randomized controlled trial. We will recruit children aged four to 11 years with a diagnosis of spastic CP (bilateral or unilateral) and Gross Motor Function Classification System (GMFCS) levels I to III who are able to comply with assessment procedures and exercise programme with or without support. Participants will be recruited from at least 12 UK NHS Trust physiotherapy and related services. Participants (n = 334) will be randomized (centralized computer-generated one:one allocation ratio) to either: 1) a dynamic stretching exercise programme, with six one-to-one physiotherapy sessions over 16 weeks; or 2) usual NHS care, with a single physiotherapy session and an assessment, and advice regarding self-management and exercise. CONCLUSION: The primary outcome is functional mobility measured using the child-/parent-reported Gait Outcomes Assessment List (GOAL) at six months. Secondary outcomes are: joint range of motion (Cerebral Palsy Integrated Pathway protocol) and motor function (timed up and go test) at six months; functional mobility (GOAL) at 12 months; independence (GOAL subdomain A); balance (GOAL subdomain A, B, D); pain and discomfort (GOAL subdomain C); health-related quality of life (youth version of the EuroQol five-dimension questionnaire (EQ-5D-Y)); educational attendance; exercise adherence; and additional physiotherapy treatment at six and 12 months. The primary analysis will be intention to treat.

Asparagine availability controls germinal center B cell homeostasis.

The rapid proliferation of germinal center (GC) B cells requires metabolic reprogramming to meet energy demands, yet these metabolic processes are poorly understood. By integrating metabolomic and transcriptomic profiling of GC B cells, we identified that asparagine (Asn) metabolism was highly up-regulated and essential for B cell function. Asparagine synthetase (ASNS) was up-regulated after B cell activation through the integrated stress response sensor GCN2. Conditional deletion of Asns in B cells impaired survival and proliferation in low Asn conditions. Removal of environmental Asn by asparaginase or dietary restriction compromised the GC reaction, impairing affinity maturation and the humoral response to influenza infection. Furthermore, metabolic adaptation to the absence of Asn required ASNS, and oxidative phosphorylation, mitochondrial homeostasis, and synthesis of nucleotides were particularly sensitive to Asn deprivation. These findings demonstrate that Asn metabolism acts as a key regulator of B cell function and GC homeostasis.

An HLA-E-targeted TCR bispecific molecule redirects T cell immunity against Mycobacterium tuberculosis.

Peptides presented by HLA-E, a molecule with very limited polymorphism, represent attractive targets for T cell receptor (TCR)-based immunotherapies to circumvent the limitations imposed by the high polymorphism of classical HLA genes in the human population. Here, we describe a TCR-based bispecific molecule that potently and selectively binds HLA-E in complex with a peptide encoded by the inhA gene of Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis in humans. We reveal the biophysical and structural bases underpinning the potency and specificity of this molecule and demonstrate its ability to redirect polyclonal T cells to target HLA-E-expressing cells transduced with mycobacterial inhA as well as primary cells infected with virulent Mtb. Additionally, we demonstrate elimination of Mtb-infected cells and reduction of intracellular Mtb growth. Our study suggests an approach to enhance host T cell immunity against Mtb and provides proof of principle for an innovative TCR-based therapeutic strategy overcoming HLA polymorphism and therefore applicable to a broader patient population.

Emulsion and liposome-based adjuvanted R21 vaccine formulations mediate protection against malaria through distinct immune mechanisms.

Adjuvanted protein vaccines offer high efficacy, yet most potent adjuvants remain proprietary. Several adjuvant compounds are being developed by the Vaccine Formulation Institute in Switzerland for global open access clinical use. In the context of the R21 malaria vaccine, in a mouse challenge model, we characterize the efficacy and mechanism of action of four Vaccine Formulation Institute adjuvants: two liposomal (LQ and LMQ) and two squalene emulsion-based adjuvants (SQ and SMQ), containing QS-21 saponin (Q) and optionally a synthetic TLR4 agonist (M). Two R21 vaccine formulations, R21/LMQ and R21/SQ, offer the highest protection (81%-100%), yet they trigger different innate sensing mechanisms in macrophages with LMQ, but not SQ, activating the NLRP3 inflammasome. The resulting in vivo adaptive responses have a different TH1/TH2 balance and engage divergent innate pathways while retaining high protective efficacy. We describe how modular changes in vaccine formulation allow for the dissection of the underlying immune pathways, enabling future mechanistically informed vaccine design.

Patient-reported outcomes as early warning signals of flare following drug cessation in rheumatoid arthritis

Clinical utility of random anti-tumor necrosis factor drug-level testing and measurement of antidrug antibodies on the long-term treatment response in rheumatoid arthritis.

OBJECTIVE: To investigate whether antidrug antibodies and/or drug non-trough levels predict the long-term treatment response in a large cohort of patients with rheumatoid arthritis (RA) treated with adalimumab or etanercept and to identify factors influencing antidrug antibody and drug levels to optimize future treatment decisions. METHODS: A total of 331 patients from an observational prospective cohort were selected (160 patients treated with adalimumab and 171 treated with etanercept). Antidrug antibody levels were measured by radioimmunoassay, and drug levels were measured by enzyme-linked immunosorbent assay in 835 serial serum samples obtained 3, 6, and 12 months after initiation of therapy. The association between antidrug antibodies and drug non-trough levels and the treatment response (change in the Disease Activity Score in 28 joints) was evaluated. RESULTS: Among patients who completed 12 months of followup, antidrug antibodies were detected in 24.8% of those receiving adalimumab (31 of 125) and in none of those receiving etanercept. At 3 months, antidrug antibody formation and low adalimumab levels were significant predictors of no response according to the European League Against Rheumatism (EULAR) criteria at 12 months (area under the receiver operating characteristic curve 0.71 [95% confidence interval (95% CI) 0.57, 0.85]). Antidrug antibody-positive patients received lower median dosages of methotrexate compared with antidrug antibody-negative patients (15 mg/week versus 20 mg/week; P = 0.01) and had a longer disease duration (14.0 versus 7.7 years; P = 0.03). The adalimumab level was the best predictor of change in the DAS28 at 12 months, after adjustment for confounders (regression coefficient 0.060 [95% CI 0.015, 0.10], P = 0.009). Etanercept levels were associated with the EULAR response at 12 months (regression coefficient 0.088 [95% CI 0.019, 0.16], P = 0.012); however, this difference was not significant after adjustment. A body mass index of ≥30 kg/m(2) and poor adherence were associated with lower drug levels. CONCLUSION: Pharmacologic testing in anti-tumor necrosis factor-treated patients is clinically useful even in the absence of trough levels. At 3 months, antidrug antibodies and low adalimumab levels are significant predictors of no response according to the EULAR criteria at 12 months.

Clusters of post-acute COVID-19 symptoms: a latent class analysis across 9 databases and 7 countries

A systematic review of the association between early comprehensive geriatric assessment and outcomes in hip fracture care for older people.

AIMS: Performance indicators are increasingly used to improve the quality of healthcare provided to hip fracture patients. Joint care, under orthopaedic surgeons and physicians with an interest in older patients, is one of the more common indicators of high-quality care. In this systematic review, we investigated the association between 'comprehensive geriatric assessment' and patient outcomes following hip fracture injury. METHODS: In total, 12 electronic databases and other sources were searched for evidence, and the methodological quality of studies meeting the inclusion criteria was assessed. The protocol for this suite of related systematic reviews was registered with PROSPERO (ID: CRD42023417515). RESULTS: A total of 24,591 articles were reviewed, and 39 studies met the inclusion criteria for the review, involving a total of 25,363 patients aged over 60 years with a hip fracture. There were five randomized clinical trials, three quasi-experimental studies, two non-randomized parallel group control trials, 22 pre-/post-intervention studies, and seven retrospective cohort studies, conducted between January 1992 and December 2021. The timing and content of a comprehensive geriatric assessment was ill-defined in many studies and care pathways were heterogeneous, which precluded meta-analysis of the data. Early comprehensive geriatric assessment was associated with improved outcomes in 31 of the 36 (86%) patient-reported outcomes, including improved mobility (acute/long-term), functional status, and better quality of life. In total, 155 out of 219 (70.78%) clinical outcomes derived from hospital records showed a positive association with early comprehensive geriatric review, including reduced preoperative time and length of hospital stay, reduced incidence of postoperative complications, fewer hospital readmissions, and lower mortality. CONCLUSION: Early comprehensive geriatric assessments after hip fracture in older people is associated with improved patient-reported outcomes and better clinical outcomes such as reduced incidence of complications, length of hospital stay, preoperative waiting time, and mortality. Standardization of the definitions of 'early' and 'comprehensive' geriatric assessments and consistent reporting of care pathway models would improve future evidence synthesis.

Thinking outside the pelvis: a modern approach to chronic pelvic pain

Chronic pelvic pain is a major public health problem that impacts all areas of a woman's life. The diagnosis is frequently difficult and delayed with women often presenting to a variety of specialties and undergoing multiple investigations before a diagnosis is reached. Aetiology is frequently multifactorial with both precipitating and perpetuating factors. An understanding of the role of the nervous system in chronic pain is essential both to plan appropriate management and to provide the patient with an acceptable explanation of her symptoms. Optimal management is within a multidisciplinary team who can fully address the range of factors that may maintain pelvic pain. Focussing solely on the pelvic organs and associated pathologies is likely to leave the majority of women with persistent symptoms.

Recommendations for Successful Development and Implementation of Digital Health Technology Tools

Abstract Digital health technology tools (DHTTs) have the potential to transform health care delivery by enabling new forms of participatory and personalized care that fit into patients’ daily lives. However, realizing this potential requires careful navigation of numerous challenges. This viewpoint presents the authors’ experiences and perspectives on the development and implementation of DHTTs, addressing both established practices and controversial topics. This article offers a practical guide organized into 10 recommendations derived from a multidisciplinary lecture series and associated workshop discussions on “Digital Health and Digital Biomarkers” held at the University of Luxembourg in 2023-2024. Key messages include the need to understand specific health care challenges, form interdisciplinary teams, incorporate patient feedback, select appropriate measurement technologies, ensure data integration and interoperability, apply advanced data science techniques, use scalable designs and open standards, comply with regulatory requirements, and maintain continuous evaluation and improvement. While the guide highlights essential practices, it also addresses contentious issues such as balancing innovation with regulatory compliance, addressing ethical concerns in artificial intelligence adoption, managing privacy versus the need for comprehensive data integration and open science, and managing the financial sustainability of DHTTs. The authors argue that digital health’s greatest potential lies in its ability to provide participatory and personalized care, but this requires a delicate balance between technological advances and ethical, legal, and social implications. Overall, this workshop-derived viewpoint aims to help health care professionals, engineers, developers, and researchers not only adopt best practices but also address and resolve the controversial aspects inherent in the development of DHTTs.