The Palestinian primary ciliary dyskinesia (PCD) cohort: clinical, diagnostic and genetic spectrum

Background: Diagnostic testing for PCD started in 2013 in Palestine. We aimed to describe the clinical, diagnostic and genetic spectrum of the Palestinian PCD cohort. Methods: 390 individuals with symptoms suggestive of PCD and 74 family members underwent nasal nitric oxide (nNO); and/or transmission electron microscopy (TEM); and/or PCD genetic panel or whole exome testing. Clinical characteristics were collected close to diagnosis including FEV1 GLI z-scores and BMI z-scores. Results: 82 had a definite positive PCD diagnosis (TEM and/or genetics) and 103 were highly likely (Kartagener’s and/or low nNO). Positive cases (n=82) had median age of 13.5 years (range 0-43), were highly consanguineous (95%) and 100% Arabic descent. Clinical features included persistent wet cough (95%), neonatal respiratory distress (79%), clubbing (21%) and situs inversus (41%). Lung function at diagnosis was already impaired FEV1 z-score mean -1.49 (sd=1.79) and BMI z-score mean -0.30 SD=1.4. 69 families were genotyped. 59 individuals from 42 families (60%) had mutations in 14 PCD-genes; CCDC39 (26% of families), DNAH11 (17%) and LRRC6 (12%) were the most common. 16% had mutations in candidate genes, 24% had no variants identified. 100% of variants were homozygous. TEM defects and genotype associations were as expected. Conclusions: Despite limited local resources, collaborations during the last 7-years have facilitated detailed geno- and phenotyping of one of the largest PCD cohorts globally. nNO identifies likely cases and targeted genetic testing, conducted locally, can now identify specific mutations in known families

The Palestinian primary ciliary dyskinesia population: first results of the diagnostic, and genetic spectrum

BACKGROUND: Diagnostic testing for primary ciliary dyskinesia (PCD) started in 2013 in Palestine. We aimed to describe the diagnostic, genetic and clinical spectrum of the Palestinian PCD population. METHODS: Individuals with symptoms suggestive of PCD were opportunistically considered for diagnostic testing: nasal nitric oxide (nNO) measurement, transmission electron microscopy (TEM) and/or PCD genetic panel or whole-exome testing. Clinical characteristics of those with a positive diagnosis were collected close to testing including forced expiratory volume in 1 s (FEV1) Global Lung Index z-scores and body mass index z-scores. RESULTS: 68 individuals had a definite positive PCD diagnosis, 31 confirmed by genetic and TEM results, 23 by TEM results alone, and 14 by genetic variants alone. 45 individuals from 40 families had 17 clinically actionable variants and four had variants of unknown significance in 14 PCD genes. CCDC39, DNAH11 and DNAAF11 were the most commonly mutated genes. 100% of variants were homozygous. Patients had a median age of 10.0 years at diagnosis, were highly consanguineous (93%) and 100% were of Arabic descent. Clinical features included persistent wet cough (99%), neonatal respiratory distress (84%) and situs inversus (43%). Lung function at diagnosis was already impaired (FEV1 z-score median −1.90 (−5.0–1.32)) and growth was mostly within the normal range (z-score mean −0.36 (−3.03–2.57). 19% individuals had finger clubbing. CONCLUSIONS: Despite limited local resources in Palestine, detailed geno- and phenotyping forms the basis of one of the largest national PCD populations globally. There was notable familial homozygosity within the context of significant population heterogeneity

The influence of gender and ethnicity on facemasks and respiratory protective equipment fit – a systematic review and meta-analysis

INTRODUCTION: Black, Asian and minority ethnic (BAME) people are disproportionately affected by COVID-19. Respiratory protective equipment (RPE) has conventionally been developed for a predominantly white male population that does not represent the healthcare workforce. The literature was reviewed to determine the protection offered to female and BAME users.METHODS: Five databases were searched. Eligible studies related to respirator fit in the context of anthropometrics, gender and ethnicity. Meta-analysis was performed for gender-based anthropometric differences. A priori protocol registration was not performed.RESULTS: 32 studies were included and anthropometric data was extracted from 15 studies. Meta-analysis revealed 14 anthropometric measurements were significantly smaller for females. Mean differences ranged from 0.37 mm to 22.05 mm. Gender-based anthropometric differences did not always translate to lower fit factor scores, with 12 studies reporting worse performance and fit for females and 10 reporting no gender effect. No studies provided disaggregate anthropometric data by ethnic group. Pass rates (PR) were low or moderate in 12 BAME or mixed-ethnicity cohorts. 14 studies reported associations between facial dimensions (FD) and respirator fit. Three comparative studies showed lower PR among selective BAME people. 18 studies reported RPE performance differed with model and design. Most studies did not prespecify inclusion/exclusion criteria. Small sample size and lack of justification or power calculations was a concern. Significant heterogeneity in study designs limited comparisons, particularly relating to respirator selection or availability and defining study outcomes relating to RPE performance.CONCLUSION: The literature reports on largely Caucasian or single ethnic populations, and BAME people remain under-represented, limiting comparisons between ethnic groups. Facial anthropometrics vary between gender and likely between ethnicity, which may contribute to lower PR among females and ethnic minorities, particularly Asians. There is a need for studies including a broader spectrum of ethnicities and for consideration of female and BAME users during RPE development.</p

Autologous fascial slings for stress urinary incontinence: a 17-year follow-up of a randomised controlled study

Introduction and hypothesis: safety concerns with the use of mesh in vaginal surgery have been ongoing. Autologous fascial slings (AFS) avoid foreign body complications. We compared the long-term (17-year) outcomes of two AFS repair methods—the standard sling and short sling (sling-on-string), and assessed durability and patient satisfaction of these for the treatment of stress urinary incontinence (SUI).Methods: a total of 107 patients from three urogynaecology units who had participated in a randomised controlled trial assessing standard (n = 52) and short (n = 55) slings were followed up for a median period of 17 years. Primary outcomes were Incontinence Impact Questionnaire (IIQ-7) and Urogenital Distress Inventory (UDI-6) scores to assess the impact on the quality of life and symptom distress. Logistic quantile regression was employed to compare the two methods. Secondary outcomes included long-term complications and patient satisfaction.Results: mean scores showed no statistically significant difference between the standard and short slings at the 17-year follow-up relating to IIQ and UDI scores, leakage or urgency (p &gt; 0.05). Improved bladder function was observed at 17 years compared with baseline (standard sling—IIQ scores mean difference [MD] 1.22 [CI: 0.69, 1.74], UDI scores MD 0.83 [CI: 0.70, 0.97]; short sling—IIQ score MD 1.14 [CI: 0.73, 1.54], UDI scores MD 0.54 [CI: 0.40, 0.67]) with age-related deterioration over time. Re-operation rates were low and patient satisfaction rates were high (67.2%) at follow-up.Conclusions: autologous fascial slings are an effective and durable option for management of SUI and the short sling procedure can be recommended owing to plausible surgical advantages

The impact of primary ciliary dyskinesia on female and male fertility: a narrative review

Background: primary ciliary dyskinesia (PCD) is a genetic condition affecting the structure and function of sperm flagellum and motile cilia including those in the male and female reproductive tracts. Infertility is a commonly reported feature of PCD, but there is uncertainty as to how best to counsel patients on their fertility prognosis.Objective and rationale: this review aimed to summarize the prevalence of subfertility, possible underlying mechanisms, and the success of ART in men and women with PCD. The efficacy of ART in this patient group is relatively unknown and, hence, the management of infertility in PCD patients remains a challenge. There are no previous published or registered systematic reviews of fertility outcomes in PCD.Search methods: systematic literature searches were performed in Medline, Embase, Cochrane Library, and PubMed electronic databases to identify publications between 1964 and 2022 reporting fertility outcomes in men and women with PCD. Publications were excluded if they reported only animal studies, where gender was not specified or where subjects had a medical co-morbidity also known to impact fertility. Quality of evidence was assessed by critical appraisal and application of an appraisal tool for cross-sectional studies. The primary outcomes were natural conception in men and women with PCD, and conception following ART in men and women with PCD.Outcomes: a total of 1565 publications were identified, and 108 publications were included after screening by two independent researchers. The quality of available evidence was low. The exact prevalence of subfertility in PCD is unclear but appears to be higher in men (up to 83% affected) compared to women (up to 61% affected). Variation in the prevalence of subfertility was observed between geographic populations which may be explained by differences in underlying genotype and cilia function. Limited evidence suggests subfertility in affected individuals is likely caused by abnormal cilia motion in the fallopian tubes, endometrium and efferent ductules, and dysmotile sperm. Some men and women with PCD benefited from ART, which suggests its use should be considered in the management of subfertility in this patient group. Further epidemiological and controlled studies are needed to determine the predictors of fertility and optimal management in this patient group.Wider implications: it is important that patients with PCD receive evidence-based counselling about the potential impact of their condition on their fertility prognosis and what management options may be available to them if affected. Understanding the pathophysiology and optimal management of subfertility in PCD will increase our understanding of the role of cilia and the impact of wider secondary ciliopathies on reproduction

The Palestinian primary ciliary dyskinesia population: first results of the diagnostic and genetic spectrum

Background Diagnostic testing for primary ciliary dyskinesia (PCD) started in 2013 in Palestine. We aimed to describe the diagnostic, genetic and clinical spectrum of the Palestinian PCD population. Methods Individuals with symptoms suggestive of PCD were opportunistically considered for diagnostic testing: nasal nitric oxide (nNO) measurement, transmission electron microscopy (TEM) and/or PCD genetic panel or whole-exome testing. Clinical characteristics of those with a positive diagnosis were collected close to testing including forced expiratory volume in 1 s (FEV1) Global Lung Index z-scores and body mass index z-scores. Results 68 individuals had a definite positive PCD diagnosis, 31 confirmed by genetic and TEM results, 23 by TEM results alone, and 14 by genetic variants alone. 45 individuals from 40 families had 17 clinically actionable variants and four had variants of unknown significance in 14 PCD genes. CCDC39, DNAH11 and DNAAF11 were the most commonly mutated genes. 100% of variants were homozygous. Patients had a median age of 10.0 years at diagnosis, were highly consanguineous (93%) and 100% were of Arabic descent. Clinical features included persistent wet cough (99%), neonatal respiratory distress (84%) and situs inversus (43%). Lung function at diagnosis was already impaired (FEV1 z-score median −1.90 (−5.0–1.32)) and growth was mostly within the normal range (z-score mean −0.36 (−3.03–2.57). 19% individuals had finger clubbing. Conclusions Despite limited local resources in Palestine, detailed geno- and phenotyping forms the basis of one of the largest national PCD populations globally. There was notable familial homozygosity within the context of significant population heterogeneity

The Palestinian primary ciliary dyskinesia population: first results of the diagnostic, and genetic spectrum

Diagnostic testing for primary ciliary dyskinesia (PCD) started in 2013 in Palestine. We aimed to describe the diagnostic, genetic, and clinical spectrum of the Palestinian PCD population.Individuals with symptoms suggestive of PCD were opportunistically considered for diagnostic testing: nasal nitric oxide (nNO) measurement, transmission electron microscopy (TEM), and/or PCD genetic panel or whole exome testing. Clinical characteristics of those with a positive diagnosis were collected close to testing including FEV1 GLI z-scores, and BMI z-scores.Sixty-eight individuals had a definite positive PCD diagnosis, 31 confirmed by genetic and TEM results, 23 by TEM results alone, and 14 by genetic variants alone. Forty-five individuals from 40 families had seventeen clinically actionable variants, and 4 had variants of unknown significance in 14 PCD-genes. CCDC39, DNAH11, and DNAAF11 were the most commonly mutated genes. 100% of variants were homozygous. Patients had median age of 11.2 years at diagnosis, were highly consanguineous (93%) and 100% of Arabic descent. Clinical features included persistent wet cough (99%), neonatal respiratory distress (84%), and situs inversus (43%). Lung function at diagnosis was already impaired (FEV1 z-score median -1.90 (-5.0 to 1.32)) and growth was mostly within the normal range (z-score mean= -0.36 (-3.03 to 2.57). 19% individuals had finger clubbing. Despite limited local resources, detailed geno- and phenotyping forms the basis of one of the largest national PCD populations globally. There was notable familial homozygosity within the context of significant population heterogeneity. <br/