Recommendations for uniform definitions used in newborn screening for severe combined immunodeficiency

BACKGROUND: Public health newborn screening (NBS) programs continuously evolve, taking advantage of international shared learning. NBS for severe combined immunodeficiency (SCID) has recently been introduced in many countries. However, comparison of screening outcomes has been hampered by use of disparate terminology and imprecise or variable case definitions for non-SCID conditions with T-cell lymphopenia. OBJECTIVES: This study sought to determine whether standardized screening terminology could overcome a Babylonian confusion and whether improved case definitions would promote international exchange of knowledge. METHODS: A systematic literature review highlighted the diverse terminology in SCID NBS programs internationally. While, as expected, individual screening strategies and tests were tailored to each program, we found uniform terminology to be lacking in definitions of disease targets, sensitivity, and specificity required for comparisons across programs. RESULTS: The study’s recommendations reflect current evidence from literature and existing guidelines coupled with opinion of experts in public health screening and immunology. Terminologies were aligned. The distinction between actionable and nonactionable T-cell lymphopenia among non-SCID cases was clarified, the former being infants with T-cell lymphopenia who could benefit from interventions such as protection from infections, antibiotic prophylaxis, and live-attenuated vaccine avoidance. CONCLUSIONS: By bringing together the previously unconnected public health screening community and clinical immunology community, these SCID NBS deliberations bridged the gaps in language and perspective between these disciplines. This study proposes that international specialists in each disorder for which NBS is performed join forces to hone their definitions and recommend uniform registration of outcomes of NBS. Standardization of terminology will promote international exchange of knowledge and optimize each phase of NBS and follow-up care, advancing health outcomes for children worldwide

Evidence supporting the best clinical management of patients with multimorbidity and polypharmacy: a systematic guideline review and expert consensus

This is the author accepted manuscript. The final version is available from Wiley via the DOI in this record.The complexity and heterogeneity of patients with multimorbidity and polypharmacy renders traditional disease-oriented guidelines often inadequate and complicates clinical decision making. To address this challenge, guidelines have been developed on multimorbidity or polypharmacy. To systematically analyse their recommendations, we conducted a systematic guideline review using the Ariadne principles for managing multimorbidity as analytical framework. The information synthesis included a multistep consensus process involving 18 multidisciplinary experts from seven countries. We included eight guidelines (four each on multimorbidity and polypharmacy) and extracted about 250 recommendations. The guideline addressed (i) the identification of the target population (risk factors); (ii) the assessment of interacting conditions and treatments: medical history, clinical and psychosocial assessment including physiological status and frailty, reviews of medication and encounters with healthcare providers highlighting informational continuity; (iii) the need to incorporate patient preferences and goal setting: eliciting preferences and expectations, the process of shared decision making in relation to treatment options and the level of involvement of patients and carers; (iv) individualized management: guiding principles on optimization of treatment benefits over possible harms, treatment communication and the information content of medication/care plans; (v) monitoring and follow-up: strategies in care planning, self-management and medication-related aspects, communication with patients including safety instructions and adherence, coordination of care regarding referral and discharge management, medication appropriateness and safety concerns. The spectrum of clinical and self-management issues varied from guiding principles to specific recommendations and tools providing actionable support. The limited availability of reliable risk prediction models, feasible interventions of proven effectiveness and decision aids, and limited consensus on appropriate outcomes of care highlight major research deficits. An integrated approach to both multimorbidity and polypharmacy should be considered in future guidelines.Journal of Internal MedicineKarolinska Institutet Strategic Research Area in Epidemiology (SfoEpi

Does shade improve light interception efficiency? A comparison among seedlings from shade-tolerant and -intolerant temperate deciduous tree species

• Here, we tested two hypotheses: shading increases light interception efficiency (LIE) of broadleaved tree seedlings, and shade-tolerant species exhibit larger LIEs than do shade-intolerant ones. The impact of seedling size was taken into account to detect potential size-independent effects on LIE. LIE was defined as the ratio of mean light intercepted by leaves to light intercepted by a horizontal surface of equal area. • Seedlings from five species differing in shade tolerance (Acer saccharum, Betula alleghaniensis, A. pseudoplatanus, B. pendula, Fagus sylvatica) were grown under neutral shading nets providing 36, 16 and 4% of external irradiance. Seedlings (1- and 2-year-old) were three-dimensionally digitized, allowing calculation of LIE. • Shading induced dramatic reduction in total leaf area, which was lowest in shade-tolerant species in all irradiance regimes. Irradiance reduced LIE through increasing leaf overlap with increasing leaf area. There was very little evidence of significant size-independent plasticity of LIE. • No relationship was found between the known shade tolerance of species and LIE at equivalent size and irradiance

Comparison of Group-based Outpatient Physiotherapy With Usual Care After Total Knee Replacement: a Feasibility Study For a Randomized Controlled Trial

Objective: To evaluate the feasibility of conducting a randomized controlled trial comparing group-based outpatient physiotherapy with usual care in patients following total knee replacement. Design: A feasibility study for a randomized controlled trial. Setting: One secondary-care hospital orthopaedic centre, Bristol, UK. Participants: A total of 46 participants undergoing primary total knee replacement. Interventions: The intervention group were offered six group-based exercise sessions after surgery. The usual care group received standard postoperative care. Participants were not blinded to group allocation. Outcome measures: Feasibility was assessed by recruitment, reasons for non-participation, attendance, and completion rates of study questionnaires that included the Lower Extremity Functional Scale and Knee Injury and Osteoarthritis Outcome Score. Results: Recruitment rate was 37%. Five patients withdrew or were no longer eligible to participate. Intervention attendance was high (73%) and 84% of group participants reported they were ‘very satisfied’ with the exercises. Return of study questionnaires at six months was lower in the usual care (75%) than in the intervention group (100%). Mean (standard deviation) Lower Extremity Functional Scale scores at six months were 45.0 (20.8) in the usual care and 57.8 (15.2) in the intervention groups. Conclusion: Recruitment and retention of participants in this feasibility study was good. Group-based physiotherapy was acceptable to participants. Questionnaire return rates were lower in the usual care group, but might be enhanced by telephone follow-up. The Lower Extremity Functional Scale had high responsiveness and completion rates. Using this outcome measure, 256 participants would be required in a full-scale randomized controlled trial

Overview of homocysteine and folate metabolism. With special references to cardiovascular disease and neural tube defects

This overview addresses homocysteine and folate metabolism. Its functions and complexity are described, leading to explanations why disturbed homocysteine and folate metabolism is implicated in many different diseases, including congenital birth defects like congenital heart disease, cleft lip and palate, late pregnancy complications, different kinds of neurodegenerative and psychiatric diseases, osteoporosis and cancer. In addition, the inborn errors leading to hyperhomocysteinemia and homocystinuria are described. These extreme human hyperhomocysteinemia models provide knowledge about which part of the homocysteine and folate pathways are linked to which disease. For example, the very high risk for arterial and venous occlusive disease in patients with severe hyperhomocysteinemia irrespective of the location of the defect in remethylation or transsulphuration indicates that homocysteine itself or one of its “direct” derivatives is considered toxic for the cardiovascular system. Finally, common diseases associated with elevated homocysteine are discussed with the focus on cardiovascular disease and neural tube defects

The effect of cognitive behavioral therapy for insomnia on sleep and glycemic outcomes in people with type 2 diabetes: A randomized controlled trial

Study objectives: Investigate whether aiding sleep by online cognitive behavioral therapy for insomnia (CBT-I) can improve glycemic and metabolic control, mood, quality of life (QoL) and insomnia symptoms in people with type 2 diabetes and assess the mediating role of lifestyle factors. Methods: Adults with type 2 diabetes and insomnia symptoms were randomly assigned to CBT-I or care as usual. At baseline, three and six months we assessed HbA1c as primary outcome and glycemic control, metabolic outcomes, sleep, mood and QoL as secondary outcomes. Mixed models were used to determine within-person and between-persons differences in outcomes and mediation analysis for lifestyle factors. Results: We randomized 29 participants to CBT-I and 28 to care as usual. Intention-to-treat analysis showed no significant differences in glycemic control, metabolic outcomes, anger, distress or QoL, but showed a significantly larger decrease in insomnia (−1.37(2.65: 0.09)) and depressive symptoms (−0.92(-1.77: 0.06)) and increase in BMI (0.29 kg/m2(0.00:0.57)) in the intervention compared to the control group. Only half of the intervention participants completed the CBT-I. Per protocol analysis showed a not statistically significant decrease in HbA1c (−2.10 mmol/l(-4.83:0.63)) and glucose (−0.39 mmol/l(-1.19:0.42)), metabolic outcomes and increase in QoL. Furthermore, the intervention group showed a significant decrease in insomnia (−2.22(-3.65: 0.78)) and depressive symptoms (−1.18(-2.17: 0.19)) compared to the control group. Lifestyle factors partially mediated the effect of the intervention. Conclusions: CBT-I might improve insomnia symptoms and mood, and perhaps improves glycemic control, albeit not significant, in people with type 2 diabetes and insomnia symptoms, compared to care as usual

The association between flow and oxygenation and cortical development in fetuses with congenital heart defects using a brain-age prediction algorithm.

OBJECTIVES: Presumably, changes in fetal circulation contribute to the delay in maturation of the cortex in fetuses with congenital heart defect (CHD). The aim of the current study is to analyze fetal brain development based on hemodynamic differences, using novel brain-age prediction software. METHODS: We have performed detailed neurosonography, including acquiring 3D volumes, prospectively in cases with isolated CHD from 20 weeks onwards. An algorithm that assesses the degree of fetal brain-age automatically was used to compare CHD cases to controls. We stratified CHD cases according to flow and oxygenation profiles by lesion physiology and performed subgroup analyses. RESULTS: A total of 616 ultrasound volumes of 162 CHD cases and 75 controls were analyzed. Significant differences in maturation of the cortex were observed in cases with normal blood flow toward the brain (-3.8 days, 95%CI [-5.5; -2.0], P = <.001) and low (-4.0 days, 95% CI [-6.7; -1.2] P = <.05; hypoplastic left heart syndrome[HLHS]) and mixed (-4.4 days, 95%CI [-6.4; -2.5] p = <.001) oxygen saturation in the ascending aorta (TGA) and in cardiac mixing (eg, Fallot) cases. CONCLUSION: The current study shows significant delay in brain-age in TGA and Fallot cases as compared to control cases. However, the small differences found in this study questions the clinical relevance

The association between flow and oxygenation and cortical development in fetuses with congenital heart defects using a brain-age prediction algorithm.

OBJECTIVES: Presumably, changes in fetal circulation contribute to the delay in maturation of the cortex in fetuses with congenital heart defect (CHD). The aim of the current study is to analyze fetal brain development based on hemodynamic differences, using novel brain-age prediction software. METHODS: We have performed detailed neurosonography, including acquiring 3D volumes, prospectively in cases with isolated CHD from 20 weeks onwards. An algorithm that assesses the degree of fetal brain-age automatically was used to compare CHD cases to controls. We stratified CHD cases according to flow and oxygenation profiles by lesion physiology and performed subgroup analyses. RESULTS: A total of 616 ultrasound volumes of 162 CHD cases and 75 controls were analyzed. Significant differences in maturation of the cortex were observed in cases with normal blood flow toward the brain (-3.8 days, 95%CI [-5.5; -2.0], P = <.001) and low (-4.0 days, 95% CI [-6.7; -1.2] P = <.05; hypoplastic left heart syndrome[HLHS]) and mixed (-4.4 days, 95%CI [-6.4; -2.5] p = <.001) oxygen saturation in the ascending aorta (TGA) and in cardiac mixing (eg, Fallot) cases. CONCLUSION: The current study shows significant delay in brain-age in TGA and Fallot cases as compared to control cases. However, the small differences found in this study questions the clinical relevance