Clinical Sensitivity of Cystic Fibrosis Mutation Panels in a Diverse Population.

Infants are screened for cystic fibrosis (CF) in New York State (NYS) using an IRT-DNA algorithm. The purpose of this study was to validate and assess clinical validity of the US FDA-cleared Illumina MiSeqDx CF 139-Variant Assay (139-VA) in the diverse NYS CF population. The study included 439 infants with CF identified via newborn screening (NBS) from 2002 to 2012. All had been screened using the Abbott Molecular CF Genotyping Assay or the Hologic InPlex CF Molecular Test. All with CF and zero or one mutation were tested using the 139-VA. DNA extracted from dried blood spots was reliably and accurately genotyped using the 139-VA. Sixty-three additional mutations were identified. Clinical sensitivity of three panels ranged from 76.2% (23 mutations recommended for screening by ACMG/ACOG) to 79.7% (current NYS 39-mutation InPlex panel), up to 86.0% for the 139-VA. For all, sensitivity was highest in Whites and lowest in the Black population. Although the sample size was small, there was a nearly 20% increase in sensitivity for the Black CF population using the 139-VA (68.2%) over the ACMG/ACOG and InPlex panels (both 50.0%). Overall, the 139-VA is more sensitive than other commercially available panels, and could be considered for NBS, clinical, or research laboratories conducting CF screening.

Oral Propranolol as an Alternative Therapy for Orbital Angiolymphoid Hyperplasia With Eosinophilia.

An 8-year-old female patient presented with left upper eyelid swelling and erythema. Magnetic resonance imaging revealed an orbital mass involving the left lacrimal gland with subsequent incisional biopsy leading to the diagnosis of angiolymphoid hyperplasia with eosinophilia. Initially prescribed an oral corticosteroid, alternative management was sought after 4 months due to unwanted side effects of steroid therapy. Oral propranolol (2 mg/kg/day) was initiated with concurrent steroid taper. Interval decrease in lesion size was observed on subsequent magnetic resonance imaging with complete resolution of subjective symptoms (Fig. 1). She remains stable 14 months after starting beta-blocker therapy. To our knowledge, our case is the second case report suggesting oral beta-blocker may be an alternative therapy for orbital angiolymphoid hyperplasia with eosinophilia.

Observational analysis of documentation burden and data duplication in trauma patient pathways at a major trauma centre.

OBJECTIVES: Trauma patients require extensive documentation across paper and electronic modalities. The objectives of this study were (1) to assess the documentation burden for trauma patients by contrasting entries against predetermined key information elements, dubbed 'data entry points' (DEPs) of a thorough trauma clerking, and by evaluating completeness of entries; and (2) to assess documentation for repetition using a Likert scale and through identification of copied data elements. METHODS: A 1-month retrospective observational pilot study analysing documentation within the first 24 hours of a patient's presentation to a major trauma centre. Documentation was analysed across three platforms: paper notes, electronic health record (EHR) and patient organisation system (POS) entries. Entries were assessed against predetermined DEPs, for completeness, for directly copied elements and for uniqueness (using a Likert scale). RESULTS: 30 patients were identified. The mean completeness of a clerking on paper, EHR and POS was 79%, 70% and 62%, respectively. Mean completeness decreased temporally down to 41% by the second ward round. The mean proportion of documented DEPs on paper, EHR and POS entries was 47%, 49% and 35%, respectively. 77% of POS entries contained copied elements, with a low level of uniqueness of 1.3/5. DISCUSSION: Our results show evidence of high documentation burden with unnecessary repetition of data entry in the management of trauma patients. CONCLUSION: This pilot study of trauma patient documentation demonstrates multiple inefficiencies and a marked administrative burden, further compounded by the need to document across multiple platforms, which may lead to eventual patient safety concerns.

Uncovering the Microbiota of Bagworm Metisa plana (Lepidoptera: Psychidae) in Oil Palm Plantations in Malaysia.

Bagworm Metisa plana is one of the major pests in Malaysia's oil palm plantation, with infestation resulting in huge economical loss. Currently, the microbial profile of the bagworm has yet to be study. Understanding the biology of the pest such as the bacterial community is crucial as bacteria associated with insects often provide benefits to the insect, giving the insect host a better chance of survival. Here, 16S amplicon sequencing was used to identify the bacteria community of M. plana. Additionally, two comparisons were made, the bacterial communities between two larval stages (early instar stage and late instar stage) from outbreak area; the bacterial communities of late instar stage larvae from non-outbreak between outbreak areas. From this study, it was found that the bacterial community of M. plana consisted of Proteobacteria, Actinobacteria, Bacterioidetes, Firmicutes and other minor phyla, with Proteobacteria being the most dominant phylum. Furthermore, bacterial genera of M. plana consisted of Pantoea, Curtobacterium, Pseudomonas, Massilia and other minor genera, with Pantoea being the most dominant. It was also found that the alpha and beta diversity in both comparisons were not significantly different. We present our data as a first insight towards the bacterial community of M. plana, paving a way towards understanding the biology of the bagworm M. plana.

Metisa plana adalah salah satu daripada perosak utama dalam ladang kelapa sawit Malaysia, dengan serangan yang mengakibatkan kerugian besar kepada ekonomi. Pada masa ini, profil mikrob bagworm masih belum dikaji. Memahami biologi perosak seperti komuniti bakteria adalah penting kerana bakteria yang dikaitkan dengan serangga sering memberi manfaat kepada serangga, memberikan hos serangga peluang untuk terus hidup. Penjujukan amplikon 16S digunakan untuk mengenal pasti komuniti bakteria M. plana. Selain itu, dua perbandingan telah dibuat, komuniti bakteria antara dua peringkat larva (peringkat instar awal dan peringkat instar lewat) dari kawasan wabak; komuniti bakteria larva peringkat instar lewat dari kawasan bukan wabak dan kawasan wabak. Daripada kajian ini, didapati komuniti bakteria M. plana terdiri daripada Proteobacteria, Actinobacteria, Bacterioidetes, Firmicutes dan filum kecil lain, dengan Proteobacteria merupakan filum yang paling dominan. Tambahan pula, genera bakteria M. plana terdiri daripada Pantoea, Curtobacterium, Pseudomonas, Massilia dan genera minor lain, dengan Pantoea yang paling dominan. Kajian ini juga mendapati bahawa kepelbagaian alfa dan beta dalam kedua-dua perbandingan adalah tidak jauh berbeza. Data ini dibentangkan sebagai pandangan pertama terhadap komuniti bakteria M. plana, membuka jalan ke arah memahami biologi bagworm M. plana.

3-[[(3S)-1,2,3,4-Tetrahydroisoquinoline-3-Carbonyl]Amino]Propanoic Acid (THICAPA) Is Protective Against Aß42-Induced Toxicity In Vitro and in an Alzheimer's Disease Drosophila.

Alzheimer's disease (AD) is the most prevalent type of dementia globally. The accumulation of amyloid-beta (Aß) extracellular senile plaques in the brain is one of the hallmark mechanisms found in AD. Aß42 is the most damaging and aggressively aggregating Aß isomer produced in the brain. Although Aß42 has been extensively researched as a crucial peptide connected to the development of the characteristic amyloid fibrils in AD, the specifics of its pathophysiology are still unknown. Therefore, the main objective was to identify novel compounds that could potentially mitigate the negative effects of Aß42. 3-[[(3S)-1,2,3,4-Tetrahydroisoquinoline-3-carbonyl]amino]propanoic acid (THICAPA) was identified as a ligand for Aß42 and for reducing fibrillary Aß42 aggregation. THICAPA also improved cell viability when administered to PC12 neuronal cells that were exposed to Aß42. Additionally, this compound diminished Aß42 toxicity in the current AD Drosophila model by rescuing the rough eye phenotype, prolonging the life span, and enhancing motor functions. Through next-generation RNA-sequencing, immune response pathways were downregulated in response to THICAPA treatment. Thus, this study suggests THICAPA as a possible disease-modifying treatment for AD.

Alleviatory effects of Danshen, Salvianolic acid A and Salvianolic acid B on PC12 neuronal cells and Drosophila melanogaster model of Alzheimer's disease.

ETHNOPHARMACOLOGICAL RELEVANCE: Danshen water extract (DWE), obtained from the Salvia miltiorrhiza Bunge (Family Lamiaceae) root, is usually employed in Chinese traditional medicine as treatment to cardiovascular ailments and cerebrovascular diseases. Intriguingly, the extract was also found to contain vast beneficial properties in Alzheimer's disease (AD) treatment. AIM OF THE STUDY: Alzheimer's disease is the most significant type of neurodegenerative disorder plaguing societies globally. Its pathogenesis encompasses the hallmark aggregation of amyloid-beta (Aß). Of all the Aß oligomers formed in the brain, Aß42 is the most toxic and aggressive. Despite this, the mechanism behind this disease remains elusive. In this study, DWE, and its major components, Salvianolic acid A (SalA) and Salvianolic acid B (SalB) were tested for their abilities to attenuate Aß42's toxic effects. METHODS: The composition of DWE was determined via Ultra-Performance Liquid Chromatography (UPLC). DWE, SalA and SalB were first verified for their capability to diminish Aß42 fibrillation using an in vitro activity assay. Since Aß42 aggregation results in neuronal degeneration, the potential Aß42 inhibitors were next evaluated on Aß42-exposed PC12 neuronal cells. The Drosophila melanogaster AD model was then employed to determine the effects of DWE, SalA and SalB. RESULTS: DWE, SalA and SalB were shown to be able to reduce fibrillation of Aß42. When tested on PC12 neuronal cells, DWE, SalA and SalB ameliorated cells from cell death associated with Aß42 exposure. Next, DWE and its components were tested on the Drosophila melanogaster AD model and their rescue effects were further characterized. The UPLC analysis showed that SalA and SalB were present in the brains and bodies of Drosophila after DWE feeding. When human Aß42 was expressed, the AD Drosophila exhibited degenerated eye structures known as the rough eye phenotype (REP), reduced lifespan and deteriorated locomotor ability. Administration of DWE, SalA and SalB partially reverted the REP, increased the age of AD Drosophila and improved most of the mobility of AD Drosophila. CONCLUSION: Collectively, DWE and its components may have therapeutic potential for AD patients and possibly other forms of brain diseases.

Single-Center Experience with Three Metallic Ureteral Stents (Allium® URS, Memokath™-051, and Resonance®) for Chronic Ureteral Obstruction.

Purpose: Patients with chronic ureteral obstruction (CUO) are traditionally managed with polymer stents/nephrostomy. However, these are prone to failure and require regular exchange. This study evaluates the efficacy of Allium® URS, Memokath™-051, and Resonance® metallic ureteral stents in managing patients with CUO. Methods: Following institutional approval (Imperial College Healthcare NHS Trust, UK, Registration Number SPS_045), operating theater records were reviewed to identify patients with CUO managed with Allium® URS, Memokath™-051, or Resonance® metallic ureteral stents (September 2015/July 2020). Baseline patient variables (age, gender, underlying etiology, and American Society of Anesthesiologists score) and stricture characteristics (length, level, and continuity) were extracted. Intraoperative and postoperative clinical and radiologic assessments at 6 weeks, 3 months, and then every 6 months, as well as any emergency attendances, were reviewed. The primary outcome was duration of functional stent survival. Secondary outcomes included intraoperative placement success and, as an estimate of renal function, mean serum creatinine over time. Results: One hundred twenty-nine stent insertion episodes (SIEs) (Allium® URS: 23; Memokath™-051: 48; Resonance®: 58) occurred in 76 patients (Allium® URS: 16; Memokath™-051: 31; Resonance®: 29). Kaplan-Meier estimates demonstrated that Resonance® provided superior functional stent survival. Overall median actual functional stent follow-up was 11.4 months for Allium® URS, 5.5 months for Memokath™-051, and 11.7 months for Resonance®. 47.8% of Allium® URS (11/23), 64.6% of Memokath™-051 (31/48), and 19% of Resonance® SIEs (11/58) failed. No Resonance® SIEs for benign indication ended in failure. Intraoperative placement success was high (Allium® URS: 95.7%; Memokath™-051 and Resonance®: both 100%). In the first year following SIE, creatinine ranged from +21.3% to +46.7% for Allium® URS, -7.8% to +8.9% for Memokath™-051, and -9.4% to +27.3% for Resonance®. Conclusions: Allium® URS, Memokath™-051, and Resonance® metallic ureteral stents are all viable management options of CUO. In this cohort, Resonance® provided superior functional stent survival. Prospective large-scale comparisons with long-term follow-up are needed to help inform stent choice dependent on individual patient and stricture characteristics.

Genetics of age-related macular degeneration.

PURPOSE OF REVIEW: Age-related macular degeneration (AMD) was until recently viewed as a part of the normal aging process; however, we are increasingly aware that genetic factors play a much greater role than previously suspected. This review will provide an up-to-date snapshot of the genetics of AMD to help guide our thoughts about its causes and the risk for family members. RECENT FINDINGS: Epidemiological research and basic bench research have identified pathways of oxidative stress, lipid metabolism and inflammation as playing causative roles in the pathogenesis of AMD. Emerging research is focusing on the biology of the retinal pigment epithelium as secreting pro and anti-inflammatory mediators in the eye. Antivascular endothelial growth factor therapy has dramatically improved the prognosis for neovascular or wet AMD patients. Nutritional supplementation with antioxidants and omega-3 fatty acids has provided treatment options for patients with atrophic or dry AMD. We should expect that some of the response to therapy might be genetically determined. SUMMARY: First-degree relatives of patients with AMD tend to have a higher risk of AMD. Recognizing an inherent genetic risk of AMD in these patients will improve their management and potentially help prevent blindness.

Overuse of Previsit Ultrasound in Patients Referred for Treatment of Inguinal Hernias.

Inguinal ultrasound (US) has a high sensitivity and specificity for the diagnosis of inguinal hernias but is often performed unnecessarily, adding cost and time to treatment. The aim of our study was to assess the rate and necessity of US before clinical examination by a hernia surgeon. Medical records of patients referred for an inguinal hernia from April through July 2017 were reviewed. These cases were analyzed for patient demographics, physical examination (PE) findings, previsit imaging, health-care system of surgeon, and case outcome. Twenty-nine per cent of patients had an inguinal US before visiting a surgeon. Sixty-three per cent of patients who underwent an US had a palpable hernia on PE, and 76 per cent had a positive PE by the surgeon. Patients without a hernia on referring provider's PE underwent US 59 per cent of the time. Inguinal USs are being ordered unnecessarily by referring providers. Physical examination by referring providers and surgeons should be the primary tool for diagnosis of an inguinal hernia.

Web-based grading of compressed stereoscopic digital photography versus standard slide film photography for the diagnosis of diabetic retinopathy.

PURPOSE: To evaluate the ability of Joint Photographic Experts Group (JPEG) compressed, stereoscopic, digital photography to identify clinical levels of diabetic retinopathy, detect clinically significant macular edema (CSME), and make appropriate referral recommendations as compared with Early Treatment Diabetic Retinopathy Study (ETDRS) standard film photography. DESIGN: Prospective, clinic-based, comparative photographic format validation study. PARTICIPANTS: Two hundred four eyes from 102 consecutive, new, diabetic patients with a median duration of diabetes of 12.5 years were enrolled and analyzed. METHODS: After pupillary dilation, a trained ophthalmic photographer obtained 2 sets of images: standard ETDRS, stereoscopic 7-field 35-mm film photographs and high-resolution, digital images of the same 7 standard fields (stereoscopic images of fields 1 and 2). Two masked readers graded both sets of images. The 35-mm film photographs were graded by hand using a written template. Digital photographs were compressed, uploaded to a web site, and graded by a web-based, computer-assisted ETDRS algorithm. The ETDRS level of diabetic retinopathy, presence of retinal thickening, and referral recommendation based on these 2 diagnoses were recorded and compared. MAIN OUTCOME MEASURES: The presence of CSME, ETDRS level of diabetic retinopathy, and referral threshold diabetic retinopathy. RESULTS: Film and compressed digital grading levels were compared using a simplified ETDRS categorization scheme. Film and digital gradings were highly correlated with exact agreements for level of diabetic retinopathy, CSME, and referral thresholds >87% and kappa levels >0.71. McNemar's testing found no statistically significant difference between compressed digital images and film when comparing referral thresholds (defined as the presence of CSME and/or ETDRS level > or = 61; P = 0.76). CONCLUSIONS: A modified ETDRS protocol (stereoscopic images of fields 1 and 2 only) with 16:1 JPEG image compression and computer-assisted ETDRS grading algorithm has excellent reproducibility when compared to standard ETDRS stereoscopic slide-film photography. An internet-based teleophthalmology system can correctly and reliably (kappa = 0.78) identify patients requiring referral for CSME and proliferative diabetic retinopathy (PDR; ETDRS level > or = 61).

Feasibility of a novel mHealth management system to capture and improve medication adherence among adolescents with asthma.

PURPOSE: Currently, 7.1 million children in the United States have asthma. Nonadherence to daily controller asthma medication is common, leading to more severe symptoms, overuse of rescue medication, and increased hospitalizations. The purpose of this study was to develop and evaluate the feasibility and acceptability of a novel mHealth management system composed of a sensored device, which is connected to mobile phone app that is designed to monitor and improve asthma medication adherence. PATIENTS AND METHODS: The asthma management system was designed using well-established behavioral theory. Seven adolescents aged 11-18 years were enrolled and given an adherence sensor, and four of those also received a mobile phone app with game features and reminders. Five patients completed the study, and one was lost to follow-up in each group. Mobile app users and their parents participated in focus groups to assess patient preferences. Feasibility was assessed by the ability of sensors to capture real-time medication data. Acceptability was assessed by patient questionnaire and focus group analysis. RESULTS: Successful upload of real-time data from six of seven inhaler sensors to the HIPAA-compliant server demonstrates the feasibility of at-home patient monitoring using the sensor device. All three mobile app users who completed the study reported interest in continued use of the management system and would recommend the app to friends. Unstructured interviews and focus groups revealed that patients felt that the intervention helped their sense of asthma control. CONCLUSION: This study demonstrates the feasibility of using the sensor device to remotely monitor real-time medication usage, and user feedback demonstrates the acceptability of the intervention for patient use. The findings provide guidance for the improvement of study design and technology development. Further research is needed to assess the efficacy of the intervention.

Comparison of stereoscopic digital imaging and slide film photography in the identification of macular degeneration.

BACKGROUND: This study compared the sensitivity and specificity of stereoscopic digital photography of the retina through a dilated pupil with a 45 degrees nonmydriatic camera and Joint Photographic Experts Group (JPEG) compression of the images with the sensitivity and specificity of 35-mm slide film photography in the identification of age-related macular degeneration (AMD). METHODS: Consecutive patients with a diagnosis of AMD were enrolled. Stereoscopic retinal images of the disc, macula and temporal macula were captured with a digital 45 degrees nonmydriatic camera (then compressed into JPEG format) and with a standard fundus camera and slide film. A single retinal specialist graded both image formats in masked fashion, at least 1 month apart, using a modified Age-Related Eye Disease Study (AREDS) severity scale. The digital images were displayed on a monitor and viewed with the use of liquid crystal display shutter glasses and stereo imaging software. The film images were mounted on a light box and graded with the use of a stereoviewer. Primary outcome measures included the presence or absence of AMD pathological features. Positive and negative predictive values (PPVs and NPVs), sensitivity, specificity and weighted kappaw statistics were calculated. RESULTS: We photographed 203 eyes (of 103 patients) with both digital and slide film cameras. Correlation of the 2 image formats was substantial in identifying AREDS level 3a or greater (kappaw=0.64, standard error=0.08, PPV=0.95, NPV=0.66, sensitivity=0.93, specificity=0.74) and excellent in identifying level 4b or greater (kappaw=0.83, standard error=0.05, PPV=0.81, NPV=0.98, sensitivity=0.94, specificity=0.94). INTERPRETATION: High-resolution stereoscopic, mydriatic, 45 degrees digital images captured with a nonmydriatic camera and JPEG compressed correlate well with stereoscopic slide film photographs in the identification of moderate to advanced AMD (AREDS level 3a or greater).

Maximal expiratory flow at FRC (V'maxFRC): Methods of selection and differences in reported values.

We compared three methods of reporting maximal expiratory flow (V'maxFRC) measured in partial expiratory flow-volume curves (PEFVCs) at the point of functional residual capacity (FRC). PEFVCs were obtained with the rapid thoracoabdominal compression technique (RTC) on a total of 446 occasions in 281 HIV-negative, asymptomatic infants (4.8-28.1 months old). Three different expressions of V'maxFRC were recorded: 1) the highest measured flow (maxV'FRC), 2) the mean of the three highest flows (mean3V'FRC), and 3) the flow at FRC in a composite curve (compV'FRC) consisting of PEFVCs, obtained at different jacket pressures and superimposed at their distal limb. The numerical value of maxV'FRC was 7.4% (+/-5.6%) higher than the mean3V'FRC, and 11.9% (+/-17.7%) higher than the compV'FRC; the mean3V'FRC was 5% (+/-18.3%) higher than the compV'FRC. Bland-Altman analysis was used to evaluate the agreement between the three indices. The mean difference and 95% limits of agreement were: maxV'FRC -mean3V'FRC, 14 +/- 18 ml/sec; maxV'FRC - compV'(FRC), 23 +/- 58 ml/sec; and mean3V'(FRC) - compV'(FRC), 10 +/- 52 ml/sec. The differences between the slopes of the three indices (regressed against height) were statistically significant, although clinically unimportant. We conclude that despite their high correlation, the mean3V'FRC and maxV'FRC should not be used interchangeably, and that the composite analysis, although useful, does not improve the reproducibility of V'maxFRC, and thus it cannot be recommended for routine use in its current form.

Intrabronchial valves for treatment of alveolar-pleural fistula in a patient with Pneumocystis jirovecii pneumonia.

Alveolo-pleural fistula is a common complication of severe pulmonary infection. Some patients require long-term placement of chest tubes until spontaneous closure of the fistula takes place, whereas others require surgical intervention. We report a case of a patient with alveolo-pleural fistula secondary to Pneumocystis jirovecii pneumonia who was successfully treated with the use of intrabronchial unidirectional valves inserted using flexible bronchoscopy.

Deaths in the Cook County jail: 10-year report, 1995-2004.

The aims of this study were to describe causes of death during the 10-year period between 1995 and 2004 in a large urban jail in Chicago; to compare disease specific mortality rates between the jail population and the general population; to explore demographic and incarceration characteristics of the inmates who died in the jail by cause of death; and to examine gender difference in demographic characteristics, incarceration patterns, and causes of death. A total of 178 deaths occurring in the jail over a 10-year period (1995-2004) were reviewed. Age-adjusted disease-specific mortality rates were computed for the jail population and compared with the rates in the US general population. Cause of death, demographic variables, and incarceration related factors were retrieved from multiple computerized databases. Descriptive analyses were performed to examine demographic and incarceration-related patterns by cause of death and gender. Heart disease was the most frequent cause of death in the jail population, followed by cerebrovascular disease and suicide. Mortality rates for heart diseases, infectious/inflammatory conditions and suicide were higher for jail inmates than the general population. Black inmates accounted for the majority of deaths due to illnesses and homicide, and a much higher proportion of white and Hispanic inmates were involved in suicide deaths. Deaths due to drug overdose or withdrawal were disproportionately higher among female inmates compared with male inmates. Consistent review of mortality rates and causes of deaths in jail can be a useful tool to better understand health issues and needs of jail inmates. Surveillance of acute and chronic illnesses and strategic reengineering of jail health care is a key to quality improvement for incarcerated populations for whom the jail system becomes their primary care provider.