Correction: Diagnostic value of partial exome sequencing in developmental disorders.

[This corrects the article DOI: 10.1371/journal.pone.0201041.].

Diagnostic value of partial exome sequencing in developmental disorders.

Although intellectual disability is one of the major indications for genetic counselling, there are no homogenous diagnostic algorithms for molecular testing. While whole exome sequencing is increasingly applied, we questioned whether analyzing a partial exome, enriched for genes associated with Mendelian disorders, might be a valid alternative approach that yields similar detection rates but requires less sequencing capacities. Within this context 106 patients with different intellectual disability forms were analyzed for mutations in 4.813 genes after pre-exclusion of copy number variations by array-CGH. Subsequent variant interpretation was performed in accordance with the ACMG guidelines. By this, a molecular diagnosis was established in 34% of cases and candidate mutations were identified in additional 24% of patients. Detection rates of causative mutations were above 30%, regardless of further symptoms, except for patients with seizures (23%). We did not detect an advantage from partial exome sequencing for patients with severe intellectual disability (36%) as compared to those with mild intellectual disability (44%). Specific clinical diagnoses pre-existed for 20 patients. Of these, 5 could be confirmed and an additional 6 cases could be solved, but showed mutations in other genes than initially suspected. In conclusion partial exome sequencing solved >30% of intellectual disability cases, which is similar to published rates obtained by whole exome sequencing. The approach therefore proved to be a valid alternative to whole exome sequencing for molecular diagnostics in this cohort. The method proved equally suitable for both syndromic and non-syndromic intellectual disability forms of all severity grades.

Consequence of delegating medication-related tasks from physician to clinical pharmacist in an acute admission unit: an analytical study.

OBJECTIVES: Studies have shown that medication histories obtained by clinical pharmacists (CPs) are more complete, and that medication reviews by CPs reduce healthcare costs, drug-related readmissions and emergency readmissions. The aim of this study was to identify the consequences of delegating medication-related tasks from physicians to CPs. METHODS: An analytical study based on data from a prospective cluster randomised trial was performed. The intervention consisted of CPs obtaining medication history, performing medication reconciliation and medication review. The physician had to approve the prescriptions and assess changes proposed by the CP. The primary outcome measure was a comparison of changes in the Electronic Medication Module (EMM) and changes proposed by CPs. RESULTS: 232 and 216 patients were included on control days (n=63) and intervention days (n=63). In total, 1018 changes were made in the control group (by physicians). In the intervention group 2123 changes were made, 1808 by CPs and 315 by physicians. In particular, the number of substitutions, registration of drugs and change of instructions for use (eg, administration times) differed between physicians and pharmacists. CPs made 341 written proposals in the intervention group and, of these, 22.9% (95% CI 18.7% to 27.8%) and 50.9% (95% CI 45.5% to 56.2%) were accepted by a physician at discharge from the acute admission unit (AAU) and hospital, respectively. CONCLUSIONS: CPs updated the EMM more thoroughly than physicians, especially entering new prescriptions, substitutions and changing instructions for use. Half of the written proposals were accepted. The extent to which patients benefit from a CP intervention is unknown.

Impact of clinical pharmacist intervention on length of stay in an acute admission unit: a cluster randomised study.

OBJECTIVES: Physicians in acute admission units (AAUs) are obliged to obtain medication history and perform medication reconciliation, which is time consuming and often incomplete. Studies show that clinical pharmacists (CPs) can obtain accurate medication histories, but so far no studies have investigated the effect of this on time measures. Therefore, the objective of the present study was to investigate the effect of a CP intervention on length of stay (LOS) in an AAU. METHODS: The study was designed as a prospective, cluster randomised study. Weekdays were randomised to control or intervention. CP intervention consisted of obtaining medication history and performing medication reconciliation and review. The primary outcome was LOS in the AAU. Secondary outcomes were other time-related measures-for example, physicians' self-reported time spent on medication topics. Finally, the number of documented medications per patient was established. RESULTS: 232 and 216 patients, respectively, were included on control (n=63) and intervention (n=63) days. The mean LOS was 342 (95% CI 323 to 362) min in the intervention group and 339 (95% CI 322 to 357) min in the control group, which was not statistically significantly different. Physicians spent on average 4.3 (95% CI 3.7 to 5.0) min in the intervention group and 7.5 (95% CI 6.6 to 8.5) min in the control group, corresponding to an overall reduction of 43.0% (95% CI 30.9% to 53.0%, p<0.001). The number of documented medications per patient was 10.0 (intervention group) and 8.8 (control group). CONCLUSIONS: This study indicates that LOS in the AAU was not affected by CP intervention; however, physicians reported a significant reduction in time spent on medication topics. TRIAL REGISTRATION NUMBER: Clinical Trial Gov: 1-16-02-379-13.

Pulmonary infections in swine induce altered porcine surfactant protein D expression and localization to dendritic cells in bronchial-associated lymphoid tissue.

Surfactant protein D (SP-D) is a pattern-recognition molecule of the innate immune system that recognizes various microbial surface-specific carbohydrate and lipid patterns. In vitro data has suggested that this binding may lead to increased microbial association with macrophages and dendritic cells. The aim of the present in vivo study was to study the expression of porcine SP-D (pSP-D) in the lung during different pulmonary bacterial infections, and the effect of the routes of infection on this expression was elucidated. Furthermore, the aim was to study the in vivo spatial relationship among pSP-D, pathogens, phagocytic cells and dendritic cells. Lung tissue was collected from experimental and natural bronchopneumonias caused by Actinobacillus pleuropneumoniae or Staphylococcus aureus, and from embolic and diffuse interstitial pneumonia, caused by Staph. aureus or Arcanobacterium pyogenes and Streptococcus suis serotype 2, respectively. By comparing normal and diseased lung tissue from the same lungs, increased diffuse pSP-D immunoreactivity was seen in the surfactant in both acute and chronic bronchopneumonias, while such increased expression of pSP-D was generally not present in the interstitial pneumonias. Co-localization of pSP-D, alveolar macrophages and bacteria was demonstrated, and pSP-D showed a patchy distribution on the membranes of alveolar macrophages. SP-D immunoreactivity was intracellular in dendritic cells. The dendritic cells were identified by their morphology, the absence of macrophage marker immunoreactivity and the presence of dendritic cell marker immunoreactivity. Increased expression of pSP-D in the surfactant coincided with presence of pSP-D-positive dendritic cells in bronchus-associated lymphoid tissue (BALT), indicating a possible transport of pSP-D through the specialized M cells overlying (BALT). In conclusion, we have shown that pSP-D expression in the lung surfactant is induced by bacterial infection by an aerogenous route rather than by a haematogenous route, and that the protein interacts specifically with alveolar macrophages and with dendritic cells in microbial-induced BALT. The function of the interaction between pSP-D and dendritic cells in BALT remain unclear, but pSP-D could represent a link between the innate and adaptive immune system, facilitating the bacterial antigen presentation by dendritic cells in BALT.