The use of CBF alone to screen which biopsies should have EM will result in a significant number of missed diagnoses. Ciliary beat pattern analysis is a more sensitive and specific test for PCD with higher PPV and NPV.

Primary ciliary dyskinesia (PCD) is an inherited chronic respiratory obstructive disease with randomized body laterality and infertility, resulting from cilia and sperm dysmotility. PCD is characterized by clinical variability and extensive genetic heterogeneity, associated with different cilia ultrastructural defects and mutations identified in >20 genes. Next generation sequencing (NGS) technologies therefore present a promising approach for genetic diagnosis which is not yet in routine use. We developed a targeted panel-based NGS pipeline to identify mutations by sequencing of selected candidate genes in 70 genetically undefined PCD patients. This detected loss-of-function RSPH1 mutations in four individuals with isolated central pair (CP) agenesis and normal body laterality, from two unrelated families. Ultrastructural analysis in RSPH1-mutated cilia revealed transposition of peripheral outer microtubules into the ‘empty’ CP space, accompanied by a distinctive intermittent loss of the central pair microtubules. We find that mutations in RSPH1, RSPH4A and RSPH9, which all encode homologs of components of the ‘head’ structure of ciliary radial spoke complexes identified in Chlamydomonas, cause clinical phenotypes that appear to be indistinguishable except at the gene level. By high-resolution immunofluorescence we identified a loss of RSPH4A and RSPH9 along with RSPH1 from RSPH1-mutated cilia, suggesting RSPH1 mutations may result in loss of the entire spoke head structure. CP loss is seen in up to 28% of PCD cases, in whom laterality determination specified by CP-less embryonic node cilia remains undisturbed. We propose this defect could arise from instability or agenesis of the ciliary central microtubules due to loss of their normal radial spoke head tethering.

The Regionalization of Perinatal Care, an intervention study carried out in Tanjungsari, a subdistrict in rural West Java, aimed to develop a comprehensive maternal health program to improve maternal and perinatal health outcomes. The main inputs included training at all levels of the health care system (informal and formal) and the establishment of birthing homes in villages to make services more accessible. Special attention was given to referral, transportation, communication and appropriate case management, A social marketing program was conducted to inform people of the accessible birthing homes for clean delivery, located near the women, and with better transportation and communications to referral facilities should complications arise. The study design was longitudinal, following all pregnant women from early pregnancy until 42 days postpartum in an intervention and a comparison area. The population was +/- 90,000 in the intervention area and 40,000 in the comparison area. Inclusion criteria were all mother and infant units delivered between June 1st, 1992 and May 31st, 1993. Analysis showed the following results: Most women sought antenatal care (> 95%). In Tanjungsari, nearly 90% sought such care from professional providers as versus 75% in the control area of Cisalak. Most women with bleeding or bleeding and edema during pregnancy sought professional assistance in both the study and control areas. However, fever for more than 3 days received more attention in the study area versus control area (93 vs. 69%). Greater than 85% of deliveries in both areas were conducted by TBAs. However, in the study area, nearly one-third of those with intrapartum complications (17%) delivered in a health facility compared to one-tenth in the control area. This meant a hospital delivery, primarily with assistance of a doctor or doctor/midwife combination. Overall referral rates by TBAs were low -13% of women with complications in Tanjungsari and 6% in Cisalak. More women with intrapartum complications were referred in the study area than in the control, and more complied when referred. Women who suffered intrapartum complications were more likely to have a perinatal death. Perinatal deaths declined in Tanjungsari, but not significantly. However, the trend over the period of the intervention shows an improvement in the deliveries managed by TBAs with more deaths resulting in the hands of professionals. Either women were arriving too late or the quality of care could not meet the needs. There was no change in the levels or place of perinatal deaths in Cisalak.

Background‘Frailty crises’ are a common cause of hospital admission among older people and there is significant focus on admission avoidance. However, identifying frailty before a crisis occurs is challenging, making it difficult to effectively target community services. Better longer-term outcome data are needed if services are to reflect the needs of the growing population of older people with frailty.AimTo determine long-term outcomes of older people discharged from hospital following short (<72 hours) and longer hospital admissions compared by frailty status.Design and settingTwo populations aged ≥70 years discharged from hospital units: those following short ‘ambulatory’ admissions (<72 hours) and those following longer inpatient stays.MethodData for 2-year mortality and hospital use were compared using frailty measures derived from clinical and hospital data.ResultsMortality after 2 years was increased for frail compared with non-frail individuals in both cohorts. Patients in the ambulatory cohort classified as frail had increased mortality (Rockwood hazard ratio 2.3 [95% confidence interval {CI} = 1.5 to 3.4]) and hospital use (Rockwood rate ratio 2.1 [95% CI = 1.7 to 2.6]) compared with those patients classified as non-frail.ConclusionIndividuals with frailty who are discharged from hospital experience increased mortality and resource use, even after short ‘ambulatory’ admissions. This is an easily identifiable group that is at increased risk of poor outcomes. Health and social care systems might wish to examine their current care response for frail older people discharged from hospital. There may be value in a ‘secondary prevention’ approach to frailty crises targeting individuals who are discharged from hospital.