Biologic drug survival rates in the era of anti-interleukin-17 antibodies: a time-period-adjusted registry analysis.

BACKGROUND: Drug survival rates reflect efficacy and safety and may be influenced by the availability of alternative treatment options. Little is known about time-dependent drug survival in psoriasis and the effect of increasing numbers of biologic treatment options. OBJECTIVES: To determine whether drug survival is influenced by the availability of treatment options and by factors such as gender, psoriatic arthritis or previous biologic treatment. METHODS: This observational, retrospective, multicentre cohort study analysed data from patients registered in the Austrian Psoriasis Registry (PsoRA) who were treated with biologics between 1 January 2015 and 30 November 2019. RESULTS: A total of 1572 patients who received 1848 treatment cycles were included in this analysis. The highest long-term Psoriasis Area and Severity Index improvement was observed after treatment with ixekizumab, followed by ustekinumab and secukinumab, adalimumab and etanercept. Overall, ustekinumab surpassed all other biologics in drug survival up to 48 months. However, when adjusted for biologic naïvety, its superiority vanished and drug survival rates were similar for ixekizumab (91·6%), secukinumab (90·2%) and ustekinumab (92·8%), all of them superior to adalimumab (76·5%) and etanercept (71·9%) at 12 months and beyond. Besides biologic non-naïvety (2·10, P < 0·001), the introduction of a new drug such as secukinumab or ixekizumab (relative hazard ratio 1·6, P = 0·001) and female gender (1·50, P = 0·019) increased the risk of treatment discontinuation overall, whereas psoriatic arthritis did not (1·12, P = 0·21). CONCLUSIONS: The time-dependent availability of drugs should be considered when analysing and comparing drug survival. Previous biologic exposure significantly influences drug survival. Women are more likely to stop treatment.

The use of online video consultations in the aftercare of orthopedic patients: a prospective case-control study.

BACKGROUND: Video consultations have proven to be an efficient source of support for patient-doctor interactions and have become increasingly used in orthopedics, especially during the COVID-19 pandemic. This study analyzed both patients' and doctors' acceptance of an orthopedic telemedical consultation (OTC) and compared the results of OTC examinations to the results of live consultation (LC) to identify discrepancies. METHODS: The study was carried out in an orthopedic department of a German hospital between 2019 and 2020. After written informed consent was obtained, patients voluntarily presented for follow-up by OTC and LC. The experience with and attitudes toward OTC among both patients and doctors was evaluated (using Likert scale-scored and open questions, 26 to 28 items). The results of the OTC and LC examinations were compared using a 12-item checklist. The data were analyzed by quantitative and qualitative statistics. RESULTS: A total of 53 patients were included, each of whom completed an OTC and an LC. The OTC was rated as pleasant, and the experience was rated as very satisfying (average rating on a 5-point Likert scale, with 1 indicating strong agreement: doctors: 1.2; patients: 1.3). Various technical and organizational challenges were identified. Compared to LC, OTC showed no significant differences in patient history or in inspection, palpation, or active range of motion results. Only for the functional or passive joint assessment did LC show significantly higher suitability (p < 0.05) than OTC. Recommendations for further procedures did not differ significantly between OTC and LC. CONCLUSIONS: Because of the high acceptance and the objective benefits of OTC and the similarity of clinical results with LC, OTC is recommendable for orthopedic follow-up examinations. To better assess joint functionality, meaningful digital alternatives for established examination methods should be further investigated.

Water, sanitation, and hygiene (WASH) factors associated with growth between birth and 1 year of age in children in Soweto, South Africa: results from the Soweto Baby WASH study.

Interventions to reduce undernutrition and improve child growth have incorporated improved water, sanitation, and hygiene (WASH) as part of disease transmission prevention strategies. Knowledge gaps still exist, namely, when and which WASH factors are determinants for growth faltering, and when WASH interventions are most effective at improving growth. This study drew cross-sectional data from a longitudinal cohort study and used hierarchical regression analyses to assess associations between WASH factors: water index, sanitation, hygiene index, and growth: height-for-age (HAZ), weight-for-age (WAZ), weight-for-height (WHZ) at 1, 6, and 12 months postpartum among infants a priori born healthy in Soweto, Johannesburg. Household access to sanitation facilities that were not safely managed was associated with a decrease in HAZ scores at 1 month (ß = -2.24) and 6 months (ß = -0.96); a decrease in WAZ at 1 month (ß = -1.21), 6 months (ß = -1.57), and 12 months (ß = -1.92); and finally, with WHZ scores at 12 months (ß = -1.94). Counterintuitively, poorer scores on the hygiene index were associated with an increase at 1 month for both HAZ (ß = 0.53) and WAZ (ß = 0.44). Provision of safely managed sanitation at household and community levels may be required before improvements in growth-related outcomes are obtained.

Characterization of Interfacial Structure in Polymer-Fullerene Bulk Heterojunctions via

We introduce a new application of solid state NMR measurements towards characterizing the donor-acceptor interfaces within bulk heterojunction (BHJ) films. Rotational echo double resonance (REDOR) is used to measure dipolar couplings between ^{13}C nuclei on the acceptor phenyl-C_{61}-butyric acid methyl ester (PCBM) fullerene cage, which is ≈18% isotopically enriched with ^{13}C, and beta hydrogens on the donor poly(3-hexyl thiophene) (P3HT) main chain, which are >95% isotopically enriched with ^{2}H. The ^{13}C-^{2}H dipolar couplings are used for constraining possible models of molecular packing in the amorphous mixed phase of a P3HT/PCBM BHJ. The films studied are highly mixed (>80%) and have a maximum length scale of composition nonuniformity of ≈6 nm in the mixed phase, as demonstrated by ^{1}H spin diffusion NMR and supported by TEM. The REDOR results show that despite the lack of phase separation at length scales greater than ≈6 nm, neat P3HT and PCBM clusters exist on ≈3 nm size scales, and, for the average PCBM molecule, the number of nearest neighbors P3HTs is two.

Age-Related Differences in Socio-demographic and Behavioral Determinants of HIV Testing and Counseling in HPTN 043/NIMH Project Accept.

Youth represent a large proportion of new HIV infections worldwide, yet their utilization of HIV testing and counseling (HTC) remains low. Using the post-intervention, cross-sectional, population-based household survey done in 2011 as part of HPTN 043/NIMH Project Accept, a cluster-randomized trial of community mobilization and mobile HTC in South Africa (Soweto and KwaZulu Natal), Zimbabwe, Tanzania and Thailand, we evaluated age-related differences among socio-demographic and behavioral determinants of HTC in study participants by study arm, site, and gender. A multivariate logistic regression model was developed using complete individual data from 13,755 participants with recent HIV testing (prior 12 months) as the outcome. Youth (18-24 years) was not predictive of recent HTC, except for high-risk youth with multiple concurrent partners, who were less likely (aOR 0.75; 95% CI 0.61-0.92) to have recently been tested than youth reporting a single partner. Importantly, the intervention was successful in reaching men with site specific success ranging from aOR 1.27 (95% CI 1.05-1.53) in South Africa to aOR 2.30 in Thailand (95% CI 1.85-2.84). Finally, across a diverse range of settings, higher education (aOR 1.67; 95% CI 1.42, 1.96), higher socio-economic status (aOR 1.21; 95% CI 1.08-1.36), and marriage (aOR 1.55; 95% CI 1.37-1.75) were all predictive of recent HTC, which did not significantly vary across study arm, site, gender or age category (18-24 vs. 25-32 years).

Apremilast in psoriasis - a prospective real-world study.

BACKGROUND: Apremilast is a novel oral phosphodiesterase-4 inhibitor approved for psoriasis treatment. Randomized trials have documented its efficacy and safety, but data on real-world patients are scarce. OBJECTIVES: We aim to characterize psoriasis patients treated with apremilast in a real-world setting and calculate drug survival as an important measure of efficacy and compliance. METHODS: All patients with psoriasis who received apremilast between 1 April 2015 and 19 January 2017 were evaluated every 4 weeks, and we documented: age, weight, height, smoking status, family history of psoriasis, joint involvement, previous treatments, psoriasis area severity index (PASI) scores, and the onset and duration of adverse events (AE). Efficacy was analysed by PASI50, PASI75 and PASI90, reflecting the improvement of skin lesions compared to the PASI-baseline. Kaplan-Meier statistics were used for drug survival estimates. RESULTS: Forty-eight patients were included. The median apremilast drug survival was 12.5 weeks (range 1-87). Three patients (6.3%) reached PASI90, nine (18.8%) PASI75 and eight patients (16.7%) PASI50. Patient weight inversely correlated with a PASI50 response (P < 0.05, n = 37), and none of the obese patients (BMI > 30.0, n = 6) reached PASI75, compared to 32% of the non-obese patients (BMI < 30.0, n = 31). Thirty-one patients (64.6%) reported at least one AE, most frequently diarrhoea (n = 21, 43.8%), headache (n = 7, 14.6%) and joint pain (n = 5, 10.4%). CONCLUSIONS: Despite differences between real-world and trial patients, apremilast is safe and effective for the treatment of skin psoriasis in the daily practice. Up to 40% of patients will reach PASI50 or higher, but only few patients will reach PASI90. Bodyweight might affect drug efficacy.

The South African universal preschool year: a case study of policy development and implementation.

BACKGROUND: South Africa is the first sub-Saharan African country to legislate, fund and implement free preschool education. Human rights and restitution were at the forefront of the political struggle for democracy in South Africa. Levelling the playing fields by improving the school readiness of children disadvantaged by the racist policies of Apartheid is essential to the transformation of South African society. METHODS: A review of published and unpublished documents on Grade R was undertaken, and access and enrolment data come from the National Department of Basic Education's Education Management Information System (EMIS). RESULTS: A decade after initiation in 2005, 79% of 5-year-olds was enrolled in a preschool class; the vast majority of them in free public schools. Grade R is near universal and on track to becoming compulsory. It is part of the Foundation Phase (Grades 1-3) of schooling, falling under the Department of Basic Education, but also part of a broader national strategy to improve early child development under the direction of an Inter-Departmental Steering. Evaluations demonstrate wide access to Grade R and high uptake, especially in the poorest areas. However, the quality of Grade R provision in these areas is not up to standard because of low levels of funding; inadequate training, supervision, remuneration and retention of Grade R teachers; insufficient learner support materials; and inadequate monitoring and quality assurance. CONCLUSIONS: Lack of quality, amongst other factors, contributes to a widening school performance gap between children from more and less privileged areas. Quality of Grade R as well as earlier learning and subsequent years of schooling must be improved to achieve South Africa's aim to reduce poverty and inequality through, amongst others, parent and family involvement, learning in the home and preschool preparation.

Care for Child Development: an intervention in support of responsive caregiving and early child development.

BACKGROUND: An estimated 43% of children younger than 5 years of age are at elevated risk of failing to achieve their human potential. In response, the World Health Organization and UNICEF developed Care for Child Development (CCD), based on the science of child development, to improve sensitive and responsive caregiving and promote the psychosocial development of young children. METHODS: In 2015, the World Health Organization and UNICEF identified sites where CCD has been implemented and sustained. The sites were surveyed, and responses were followed up by phone interviews. Project reports provided information on additional sites, and a review of published studies was undertaken to document the effectiveness of CCD for improving child and family outcomes, as well as its feasibility for implementation in resource-constrained communities. RESULTS: The inventory found that CCD had been integrated into existing services in diverse sectors in 19 countries and 23 sites, including child survival, health, nutrition, infant day care, early education, family and child protection and services for children with disabilities. Published and unpublished evaluations have found that CCD interventions can improve child development, growth and health, as well as responsive caregiving. It has also been reported to reduce maternal depression, a known risk factor for poor pregnancy outcomes and poor child health, growth and development. Although CCD has expanded beyond initial implementation sites, only three countries reported having national policy support for integrating CCD into health or other services. CONCLUSIONS: Strong interest exists in many countries to move beyond child survival to protect and support optimal child development. The United Nations Sustainable Development Goals depend on children realizing their potential to build healthy and emotionally, cognitively and socially competent future generations. More studies are needed to guide the integration of the CCD approach under different conditions. Nevertheless, the time is right to provide for the scale-up of CCD as part of services for families and children.

Trends in HIV testing and associated factors among men in South Africa: evidence from 2005, 2008 and 2012 national population-based household surveys.

OBJECTIVES: In Sub-Saharan African countries, including South Africa, uptake of human immunodeficiency virus (HIV) testing among men remains a major challenge. Few studies have explored HIV testing uptake among men and factors that influence their testing behaviours. This article explores trends in HIV testing uptake and associated factors among men aged 15 years and older in South Africa using national HIV population-based household surveys conducted in 2005, 2008 and 2012. STUDY DESIGN: A multistage cross-sectional design was used in the three nationally representative household-based surveys. METHODS: P-trend Chi-squared statistic was used to analyze changes in HIV testing in relation to demographic factors, and HIV-related risk behaviours across the three surveys. Univariate and multivariate logistic regression models were used to assess the associations between ever testing for HIV, demographic factors and HIV-related risk behaviours. RESULTS: HIV testing uptake among men was 28% in 2005, 43% in 2008 and 59% in 2012. A trend was also observed in HIV testing by sociodemographic factors, but differences existed within variables. HIV testing uptake was mainly influenced by the effects of selected population characteristics. Reduced likelihood of HIV testing was significantly associated with males aged 15-24 years, Black African race group, being single and unemployed, those residing in urban informal and rural informal areas, and those men who ever had sex. CONCLUSION: The observed sociodemographic differentials suggest that an effective expansion strategy for HIV testing needs to prioritize those most unlikely to test as identified by the current findings.

Use of the ages and stages questionnaire adapted for South Africa and Zambia.

BACKGROUND: There are few readily available, relatively easy to use and culturally adaptable developmental assessment tools for young children in southern Africa. The overarching aim of this study is to test the psychometric properties, contextual appropriateness and cut-off scores across 21 age groups of the Ages and Stages Questionnaire Third Edition (Squires & Bricker, ) among a group of typically developing children in South Africa and Zambia through a combination of both caregiver-report and direct observations, and to compare children's performance across sociodemographic variables. METHODS: The sample consisted of 853 children (50.5% Zambia, with 50.1% girls for Zambia and 50% girls for South Africa) aged 2 months to 60 months. Information on caregiver employment, education and household assets were also obtained. RESULTS: The psychometric properties of the ASQ-3 in southern Africa are consistent with those found in the extant literature. Analysis of item difficulty at each age reveals adequate levels of difficulty for majority of the items, with exception of the problem solving domain where half of the items at 54 and 60 months have poor pass rates. Sociodemographic variables were significantly associated with children's performance: higher caregiver levels of education are associated with higher toddler scores on the personal-social domain and higher preschooler scores on the problem solving domain; children whose caregivers earn a salary have higher fine motor scores during toddlerhood and higher problem solving scores during preschool and children who attend preschools have higher gross motor scores during toddlerhood and higher fine motor scores during the preschool years. CONCLUSIONS: Findings provide evidence to support the psychometric properties and feasibility of using the ASQ-3 in both South Africa and Zambia through a combination of caregiver-report and direct observations.

Pyoderma gangrenosum during pregnancy - treatment options revisited.

BACKGROUND: Pyoderma gangrenosum (PG) is a rare, ulcerating neutrophilic dermatosis of unknown aetiology; PG during pregnancy is particularly rare. The disease is frequently associated with immune-mediated, inflammatory diseases. OBJECTIVE: Diagnosis of PG can be challenging and relies upon exclusion of other causes such as traumas, infections, vascular diseases or neoplasms. Treatment options during pregnancy are limited. METHODS: To evaluate current treatment options for PG during pregnancy, we present a case of multilocular PG during the patient's first trimester. In conjunction with a comprehensive review of previously published cases of PG during gravidity, we discuss available treatment modalities including immunosuppressants and TNFα inhibitors. RESULTS: Our patient highlights the importance of including PG as a potential differential diagnosis of cutaneous ulcers during gravidity. Treatment with systemic glucocorticoids is effective and safe for the health of the mother and the unborn. CONCLUSION: In pregnant females, it is particularly important to diagnose PG and control disease activity due to the risk of pathergy and wound healing deficiencies during delivery and post-partum. A limited number of treatment options are available to date, which require a precise risk-benefit evaluation.

[Cutaneous involvement in chronic inflammatory bowel disease : Crohn's disease and ulcerative colitis]. / Hauterscheinungen bei chronisch entzündlichen Darmerkrankungen : Morbus Crohn und Colitis ulcerosa.

BACKGROUND: Over recent decades, both the incidence and prevalence of chronic inflammatory bowel disease have continued to rise in industrialized countries; the disease is frequently associated with extracutaneous involvement and comorbidity. OBJECTIVES: The purpose of this work was to investigate the frequency and specificity of mucocutaneous manifestations in Crohn's disease (CD) and ulcerative colitis (UC). MATERIALS AND METHODS: An extensive search in peer-reviewed journals via PubMed was performed; presented is a summary and analysis of various studies and data, including data of patients treated at our department. RESULTS: CD and UC are frequently associated with mucocutaneous symptoms; however, primary/specific disease-associations are exclusively seen in CD patients. These include peri-anal and -stomal fistulas and ulcerations, "metastatic" Crohn's disease as well as oral granulomatous disease. Moreover, in both CD and UC, there occur several other inflammatory skin conditions such as erythema nodosum, pyoderma gangrenosum, hidradenitis suppurativa, chronic oral aphthous disease, Sweet syndrome, pyostomatitis vegetans, and bowel-associated dermatosis-arthritis syndrome. Malnutrition syndromes (zinc and vitamin deficiencies) are only rarely observed. CONCLUSION: On skin and oral/genital mucous membranes various different inflammatory manifestations may be observed during the course of CD or UC. However, most data about a direct pathogenic relationship of the gastrointestinal and dermatologic disorders are quite heterogeneous or even contradictory. Nevertheless, knowledge of these conditions and their possible association with CD and UC could be crucial for early diagnosis and initiation of an appropriate therapy and thus be essential to prevent secondary tissue damage.

[Systemic lupus erythematosus : Unusual cutaneous manifestations]. / Systemischer Lupus erythematodes : Ungewöhnliche Hautmanifestationen.

BACKGROUND: Various different mucocutaneous symptoms may affect up to 80 % of systemic lupus erythematosus (SLE) patients. OBJECTIVES: To investigate, various unspecific, but otherwise typical clinical symptoms of skin and mucous membranes that arise in SLE patients other than those defined as SLE criteria such as butterfly rash, chronic cutaneous lupus erythematosus, oral ulcers, and increased photosensitivity. MATERIALS AND METHODS: Extensive search of peer-reviewed scientific articles was performed, medical histories of several SLE patients seen in our department were analyzed, and the rare disease courses in three SLE patients are presented. RESULTS: Here we present a variety of unspecific but typical mucocutaneous manifestations in SLE patients: periungual erythema, periungual telangiectasia and periungual splinter hemorrhage, papules on the dorsum of the hands, scaling erythema, sometimes associated with necrosis, especially of the ears, along with complement deficiency, and the bizarre necroses of antiphospholipid syndrome. Furthermore, we show the typical clinico-histological features of neutrophilic urticarial dermatosis, as well as those of bullous SLE and finally a severe course of bacterial sepsis with Neisseria flavescens/macacae. CONCLUSIONS: Here we show several unspecific but rather typical mucocutaneous symptoms in lupus patients that are indicative of SLE and thus may lead to an early diagnosis. Also, life-threatening bacterial sepsis may occur with microorganisms that are commonly considered "apathogenic", such as Neisseria flavescens/macacae, which exclusively affect immunosuppressed patients.

Even transient rapid infancy weight gain is associated with higher BMI in young adults and earlier menarche.

BACKGROUND: Early postnatal rapid 'catch-up' weight gain has been consistently associated with subsequent higher obesity risk and earlier pubertal development. In many low- and middle-income countries, infancy catch-up weight gain is transient and often followed by growth faltering. We explored the hypothesis that even transient catch-up weight gain during infancy is associated with later obesity risk and earlier puberty. METHODS: A total of 2352 (1151 male, 1201 female) black South African children in the birth to twenty prospective birth cohort study (Johannesburg-Soweto) underwent serial measurements of body size and composition from birth to 18 years of age. At the age of 18 years, whole-body fat mass and fat-free mass were determined using dual-energy X-ray absorptiometry. Pubertal development was assessed by the research team between ages 9 and 10 years, and it was recorded annually from the age of 11 years using a validated self-assessment protocol. RESULTS: Catch-up weight gain from birth to the age of 1 year, despite being followed by growth faltering between ages 1 and 2 years, was associated with greater mid-upper arm circumference (P=0.04) and skinfold thickness (P=0.048) at 8 years of age, and with higher weight (P<0.001) and body mass index (P=0.001) at 18 years of age after adjustment for sex, age, smoking during pregnancy, birth order, gestational age, formula-milk feeding and household socio-economic status. Infancy catch-up weight gain was also associated with younger age at menarche in girls (P<0.001). This association persisted after adjustment for smoking during pregnancy, birth order, gestational age, formula-milk feeding and household socio-economic status (P=0.005). CONCLUSION: Transient catch-up weight gain from birth to the age of 1 year among children born in a low-income area of South Africa was associated with earlier menarche and greater adiposity in early adulthood. This observation suggests that modifiable determinants of rapid infancy weight gain may be targeted in order to prevent later obesity and consequences of earlier puberty in girls.

Parental childhood growth and offspring birthweight: pooled analyses from four birth cohorts in low and middle income countries.

OBJECTIVE: Associations between parental and offspring size at birth are well established, but the relative importance of parental growth at different ages as predictors of offspring birthweight is less certain. Here we model parental birthweight and postnatal conditional growth in specific age periods as predictors of offspring birthweight. METHODS: We analyzed data from 3,392 adults participating in four prospective birth cohorts and 5,506 of their offspring. RESULTS: There was no significant heterogeneity by study site or offspring sex. 1SD increase in maternal birthweight was associated with offspring birthweight increases of 102 g, 1SD in maternal length growth 0-2 year with 46 g, and 1SD in maternal height growth Mid-childhood (MC)-adulthood with 27 g. Maternal relative weight measures were associated with 24 g offspring birth weight increases (2 year- MC) and 49 g for MC-adulthood period but not with earlier relative weight 0-2 year. For fathers, birthweight, and linear/length growth from 0-2 year were associated with increases of 57 and 56 g in offspring birthweight, respectively but not thereafter. CONCLUSIONS: Maternal and paternal birthweight and growth from birth to 2 year each predict offspring birthweight. Maternal growth from MC-adulthood, relative weight from 2-MC and MC-adulthood also predict offspring birthweight. These findings suggest that shared genes and/or adequate nutrition during early life for both parents may confer benefits to the next generation, and highlight the importance of maternal height and weight prior to conception. The stronger matrilineal than patrilineal relationships with offspring birth weight are consistent with the hypothesis that improving the early growth conditions of young females can improve birth outcomes in the next generation.

Adalimumab in the treatment of moderate-to-severe chronic plaque psoriasis in patients switching from other biologics.

BACKGROUND: Ample evidence shows that switching from one biological agent to another may prove effective when response to the first one is inadequate. Nevertheless, there are little data so far showing the efficacy and safety of adalimumab in patients with plaque psoriasis who previously received another biologic agent. OBJECTIVE: We evaluated the 1-year effectiveness, safety and quality-of-life outcomes patients with psoriasis who had switched to adalimumab from other biologic therapies. METHODS: Forty-two patients who participated in this Austrian multicenter study were treated with adalimumab over a 1-year period, after switching from efalizumab, infliximab or etanercept. Effectiveness was assessed using standardized tools for measurement of disease severity [Psoriasis Area and Severity Index (PASI) and Nail Psoriasis Severity Index (NAPSI)] and quality of life [Dermatology Life Quality Index (DLQI)]. The study endpoints were evaluated using the all-treated population. RESULTS: The mean percentage of improvement at the end of the study was 74.3% for PASI, 81.6% for DLQI and 83.6% for NAPSI, demonstrating a considerable benefit of treatment with adalimumab. The safety profile observed was consistent with previous clinical trials for adalimumab, and no new safety signals were observed. CONCLUSION: Adalimumab therapy in patients with plaque psoriasis previously treated with other biologic agents demonstrates effectiveness, safety and improvement in quality of life.

[On the Differential Diagnosis of Intractable Psychogenic Chronic Cough: Neuropathic Larynx Irritable - Gabapentin's Antitussive Action]. / Zur Differenzialdiagnose des quälenden psychogenen chronischen Hustens: neuropathischer Larynx irritable - Gabapentin als Antitussivum.

We present the case of a 76 year old female inpatient who suffered from a chronic intractable cough which arose simultaneously to a severe major depression and was secondary to an exorbitant psychological distress. Chronic cough had never been experienced before and was initially considered to have a mere psychogenic origin since a comprehensive and guideline-based diagnostic screening did not reveal any underlying somatic cause. However, several factors cast doubt on the solitary psychic genesis of the chronic cough: i) occurrence immediately after a penetrant cold, ii) embedding in other complaints of laryngeal hyperreagibility (larynx irritable), such as persistent globus pharyngeus sensation, throat clearing and episodic dysphonia, iii) first occurrence on old life, iv) erupting from sleep as well, v) persistence despite remission of the major depression, and v) no sustaining benefit from specific psychotherapy and speech therapy. Therefore, diagnostics were extended to apparative tools for objective evaluation of swallowing by using fiberoptic videoendoscopic (FEES) and videofluoroscopic (VFS) techniques, which revealed signs of laryngeal neuropathy but without evidence of penetration or aspiration. A co-existing small goiter and an impaired glucose tolerance along with a putative intracellular vitamin B12 or folate deficiency (as indirectly derived from an apparent hyperhomocysteinemia) were assumed to be responsible for the neuropathy and underwent specific treatments. The impaired glucose tolerance and putative vitamin deficit were compatible with a distal symmetric sensorimotoric, even subclinical polyneuropathy of the lower extremities. The larynx irritable improved under gabapentin being confirmed by drug removals several times, and finally calmed down almost completely under gabapentin, which was in line with the scant literature of this topic. Re-examination of the larynx per FEES nine months later showed no deficits any more under the well-tolerated treatment (gabapentin, levothyroxine, vitamin B12 and folic acid substitution, weight reduction and physical training). All in all, the larynx irritable as well as the chronic cough were most probably induced by a laryngeal neuropathy and were not solely of psychic origin. Due to good treatment options a larynx irritable should be regularly taken into consideration of the investigation of intractable chronic cough. Therefore, an apparative evaluation of deglutition is recommended in the diagnostic toolbox of chronic cough - even if embedded in a psychiatric disorder or distress - before diagnosing a sole psychic origin. An hypothetical scheme of the development of a larynx irritable caused by neuropathic and non-neuropathic ("nociceptive") conditions is proposed.

The association between stunting and psychosocial development among preschool children: a study using the South African Birth to Twenty cohort data.

BACKGROUND: A large literature in developing countries finds a strong association between stunting in early childhood and educational attainment and/or cognitive performance among children of school-going age. We contribute to the literature on the effects of stunting in childhood by exploring the links between linear growth retardation and measures of development among preschool-aged children. METHODS: We analyse the association between stunting (height-for-age z-score <-2) at age 2 years and children's scores on the Vineland Social Maturity Scale (VSMS) at age 4 years, a measure of social competence or 'daily living skills', and the Revised-Denver Prescreening Developmental Questionnaire (R-DPDQ) at age 5 years, a test which places greater emphasis on cognitive functioning. The sample is drawn from the Birth to Twenty cohort study, a prospective dataset of children born in 1990 in urban South Africa. We conduct multivariate regression analysis controlling for socio-economic status, various child-specific characteristics, home environment and caregiver inputs. RESULTS: No significant association between stunting and children's performance on the VSMS, but a large and significant association with the R-DPDQ scores, was found. A disaggregated analysis of the various components of the scores suggests that children with low height-for-age at 2 years do not fall behind in terms of daily living skills or social maturity, but do substantially worse on measures capturing higher order fine motor skills and cognitive functioning. CONCLUSIONS: Stunting in early childhood is strongly related to impaired cognitive functioning in children of preschool age, but does not seem to affect social maturity, at least as measured by the VSMS. These relationships between stunting at 2 years and psychosocial development at 4 and 5 years hold with extensive controls for socio-economic status, home environment, caregiver inputs and child characteristics included in the multivariate analysis.