Histologic Features of Mycobacterial Spindle Cell Pseudotumors: A Multi-institutional Clinicopathologic Analysis of 14 Cases.

Mycobacterial spindle cell pseudotumors (MSPs) are a rare and diagnostically challenging manifestation of non-tuberculous mycobacterial (NTM) infections. Proper recognition of these pseudotumors is important because they are treatable and benign. In this study, we evaluated the morphologic patterns of MSPs to improve their pathologic identification. Clinical and morphologic features of 14 MSPs were analyzed. Histologic factors evaluated included the architectural growth pattern of spindled or epithelioid macrophages, granulomas and their location within the lesion, neutrophilic microabscesses, multinucleated giant cells, necrosis, and effacement of background tissue. The composition of inflammatory infiltrates, organism density by acid-fast staining, and stromal changes were also assessed. In addition, 8 of 14 cases underwent molecular microbiology identification by a clinical amplicon-sequencing assay for non-tuberculous mycobacteria. MSP sites included 2 bowel, 10 lymph nodes, 1 liver, and 1 extremity. Cases with available clinical history (n=10) all occurred in immunocompromised patients. All demonstrated effacement of normal structures with spindled cells arranged in a storiform or fascicular architectural pattern. In addition, all cases showed lymphocytic inflammation, with prominent concurrent neutrophilic inflammation in 50% (7/14) of cases. Other morphologic findings included foamy histiocytes (64%, 9/14), peripherally situated granulomas (21%, 3/14), and neutrophilic microabscesses (21%, 3/14). All tested cases were positive for NTM by PCR methods. Mycobacterium avium was the most commonly isolated pathogen (6/8). Mycobacterial spindle cell pseudotumors show predominantly spindled morphology that may be mistaken as a neoplasm. Surgical pathologists who evaluate lymph nodes, soft tissue, and gastrointestinal tissues should be aware of this spindled tumefactive phenomenon in the setting of immunocompromised patients. Recognition of key morphologic features of neutrophilic inflammation, peripheral granulomas, or foamy histiocytes within a spindled lesion can help guide the pathologist to a correct diagnosis of an inflammatory process secondary to infection rather than a spindle cell neoplasm. Accurate diagnosis to facilitate appropriate antimicrobial and/or surgical therapy requires a comprehensive evaluation combining clinical, histopathologic, and microbiological findings.

Association between oxidative stress, antioxidant enzymes, and homocysteine in patients with polycystic ovary syndrome.

OBJECTIVE: Polycystic ovary syndrome (PCOS) is a prevalent health condition that commonly affects adolescent girls and young women. The purpose of this study was to evaluate the correlation between levels of total glutathione (TG), reduced glutathione (GSH), superoxide dismutase (SOD), lipid peroxidation, and homocysteine with PCOS. PATIENTS AND METHODS: This study employed a cross-sectional case-control design, involving a target population of 305 Sudanese females. Among them, 205 individuals were categorized as cases, and 100 served as controls. The TG, GSH, SOD, lipid peroxidation, and homocysteine levels were measured in the serum of study participants through enzyme-linked immunosorbent essay. RESULTS: Total glutathione (1,174.5 ± 271.4 vs. 986.1 ± 191.5, p = 0.01), GSH (801.3 ± 132.2 vs. 748.6 ± 103.1, p = 0.007), SOD (225.2 ± 57.8 vs. 195.5 ± 49.6, p = 0.009), lipid peroxidation (3.4 ± 1.1 vs. 2.4 ± 0.7, p = 0.03), and homocysteine (14.9 ± 2.1 vs. 13.5 ± 1.6, p = 0.04), showed significant differences between the two groups (cases vs. controls). A moderate positive correlation between TG, GSH, SOD, lipid peroxidation, homocysteine, BMI, age, and duration of PCOS was observed. Furthermore, a strong positive correlation between BMI, age, and duration of PCOS was noted within the patient group. CONCLUSIONS: In conclusion, this study demonstrates that patients with PCOS have elevated levels of TG, GSH, SOD, lipid peroxidation, and homocysteine compared to the control group. These findings suggest a potential association between PCOS and oxidative stress, lipid metabolism, and homocysteine pathways. Moreover, the observed positive correlation with BMI, age, and duration of PCOS indicates the importance of these factors in disease progression.

Evaluation of Forced Expiratory Volume in One Second and Forced Vital Capacity from Age and Height for Pulmonary Function Test.

BACKGROUND: Lung function tests (LFTs) are a collection of clinical examinations used to assess lung function and monitor potential declines in the lungs, respiratory muscles, and chest wall's mechanical performance. This cross-sectional study aimed to identify the relation of age and height to lung function. MATERIAL AND METHODS: The study was conducted at AlHussein Medical City, 70 adult male subjects were enrolled in the study. All subjects were screened physically to ensure that they were normal and there were no respiratory disorders that could affect the lung function. Age and height were taken for these subjects, forced vital capacity (FVC), FEV1 (Forced expiratory volume in first second) as well as FEV1 /FVC ratio were measured. RESULTS: The results of the study showed that the average values of FVC and FEV1 were 4.75 and 3.88 respectively. There was a significant negative correlation observed between age and FVC (r=0.48), FEV1 (r= 0.6). Also there was a significant positive correlation noticed between Height and FVC (r = 0.62), FEV1 (r =0.69). There was a very high correlation evidenced between FEV1 and FVC, the relation between FEV1 and FVC is practically height and age-independent. CONCLUSION: Our study highlights a great interest in the study of the relation between age, height, and lung function. The study also creates simple and convenience equations that can be used for reference standards in clinical practice to give reasonable theoretical values for a large sector of the population.

CONTEXTE: Les tests de fonction pulmonaire (TFP) regroupent une série d'examens cliniques utilisés pour évaluer la fonction pulmonaire et surveiller d'éventuelles réductions des performances mécaniques des poumons, des muscles respiratoires et de la paroi thoracique. Cette étude transversale visait à déterminer la relation entre l'âge et la taille et la fonction pulmonaire. MATÉRIEL ET MÉTHODES: L'étude a été menée à la ville médicale Al-Hussein. Soixante-dix sujets masculins adultes ont été inscrits à l'étude. Tous les sujets ont été soumis à un examen physique pour s'assurer qu'ils étaient en bonne santé et ne présentaient pas de troubles respiratoires susceptibles d'affecter la fonction pulmonaire. L'âge et la taille de ces sujets ont été relevés, et la capacité vitale forcée (CVF), le VEMS (volume expiratoire maximal en une seconde) ainsi que le rapport VEMS/CVF ont été mesurés. RÉSULTATS: Les résultats de l'étude ont montré que les valeurs moyennes de la CVF et du VEMS étaient respectivement de 4,75 et 3,88. Une corrélation négative significative a été observée entre l'âge et la CVF (r = 0,48) ainsi qu'entre l'âge et le VEMS (r = 0,6). De plus, une corrélation positive significative a été remarquée entre la taille et la CVF (r = 0,62) ainsi qu'entre la taille et le VEMS (r = 0,69). Une corrélation très élevée a été mise en évidence entre le VEMS et la CVF, la relation entre le VEMS et la CVF est pratiquement indépendante de la taille et de l'âge. CONCLUSION: Notre étude met en évidence un intérêt particulier pour l'étude de la relation entre l'âge, la taille et la fonction pulmonaire. L'étude crée également des équations simples et pratiques qui peuvent être utilisées comme référence dans la pratique clinique pour fournir des valeurs théoriques raisonnables pour une grande partie de la population. Mots-clés: VEMS, CVF, VEMS/CVF, Spirométrie.

44-year temporal trends and causes of maternal mortality at the Lagos University Teaching Hospital, LUTH, Lagos, Nigeria (1976-2019).

Background: Nigeria has committed to global initiatives aimed at improving maternal and child health. Institutional audit of maternal mortality over a long period can provide useful information on the trends in maternal death and the impact of interventions. Aim: To evaluate the trends in annual deliveries, maternal mortality ratio and causes of maternal death at a tertiary institution in Nigeria over a period of 44 years (1976-2019). Materials and Methods: We conducted a temporal trend analysis of annual births, maternal deaths, maternal mortality ratio (MMR), and ranking of causes of maternal deaths at a Teaching Hospital, in Southwest Nigeria using available data from 1976 to 2019. Overall and segmental annual percent change (APC) of the observed trends were conducted using Joinpoint version 4.5.0.1 software. Results: Over the 44-year study period, 1323 maternal deaths occurred at approximately 30 maternal deaths per annum. There was a four-fold increase in MMR from 881/100,000 total births in 1976 to 3389.8/100,000 total births in 2019, at an average increase of 3.1% per annum. (APC: 3.1%; P value < 0.001). The leading causes of maternal mortality were hypertension, sepsis, haemorrhage, and abortion, which together contributed to more than 70% of maternal deaths. All the leading causes of maternal deaths except abortion had constant ranking during the study period. Conclusion: The four-fold increase in MMR at our hospital from 1976-2019 is worrying and may suggest that previous efforts at reducing maternal mortality in our institution did not lead to significant improvement toward the attainment of Sustainable Development Goal 3 (SDG3). The hospital increasingly managed complex cases especially the unbooked patients who were referred to the hospital as a last resort.

Ultrasensitive Detection of Circulating LINE-1 ORF1p as a Specific Multicancer Biomarker.

Improved biomarkers are needed for early cancer detection, risk stratification, treatment selection, and monitoring treatment response. Although proteins can be useful blood-based biomarkers, many have limited sensitivity or specificity for these applications. Long INterspersed Element-1 (LINE-1) open reading frame 1 protein (ORF1p) is a transposable element protein overexpressed in carcinomas and high-risk precursors during carcinogenesis with negligible expression in normal tissues, suggesting ORF1p could be a highly specific cancer biomarker. To explore ORF1p as a blood-based biomarker, we engineered ultrasensitive digital immunoassays that detect mid-attomolar (10-17 mol/L) ORF1p concentrations in plasma across multiple cancers with high specificity. Plasma ORF1p shows promise for early detection of ovarian cancer, improves diagnostic performance in a multianalyte panel, provides early therapeutic response monitoring in gastroesophageal cancers, and is prognostic for overall survival in gastroesophageal and colorectal cancers. Together, these observations nominate ORF1p as a multicancer biomarker with potential utility for disease detection and monitoring. SIGNIFICANCE: The LINE-1 ORF1p transposon protein is pervasively expressed in many cancers and is a highly specific biomarker of multiple common, lethal carcinomas and their high-risk precursors in tissue and blood. Ultrasensitive ORF1p assays from as little as 25 µL plasma are novel, rapid, cost-effective tools in cancer detection and monitoring. See related commentary by Doucet and Cristofari, p. 2502. This article is featured in Selected Articles from This Issue, p. 2489.

Ultrasensitive detection of circulating LINE-1 ORF1p as a specific multi-cancer biomarker.

Improved biomarkers are needed for early cancer detection, risk stratification, treatment selection, and monitoring treatment response. While proteins can be useful blood-based biomarkers, many have limited sensitivity or specificity for these applications. Long INterspersed Element-1 (LINE-1, L1) open reading frame 1 protein (ORF1p) is a transposable element protein overexpressed in carcinomas and high-risk precursors during carcinogenesis with negligible detectable expression in corresponding normal tissues, suggesting ORF1p could be a highly specific cancer biomarker. To explore the potential of ORF1p as a blood-based biomarker, we engineered ultrasensitive digital immunoassays that detect mid-attomolar (10-17 M) ORF1p concentrations in patient plasma samples across multiple cancers with high specificity. Plasma ORF1p shows promise for early detection of ovarian cancer, improves diagnostic performance in a multi-analyte panel, and provides early therapeutic response monitoring in gastric and esophageal cancers. Together, these observations nominate ORF1p as a multi-cancer biomarker with potential utility for disease detection and monitoring.

Vascular invasion predicts the subgroup of lung adenocarcinomas ≤2.0 cm at risk of poor outcome treated by wedge resection compared to lobectomy.

Background: Recent randomized control trials (JCOG0802 and CALGB140503) have shown sublobar resection to be noninferior to lobectomy for non-small cell lung cancer (NSCLC) ≤2.0 cm. We have previously proposed histologic criteria stratifying lung adenocarcinoma into indolent low malignant potential (LMP) and aggressive angioinvasive adenocarcinomas, resulting in better prognostication than provided by World Health Organization grade. Here we determine whether pathologic classification is reproducible and whether subsets of adenocarcinomas predict worse outcomes when treated by wedge resection compared to lobectomy. Methods: A retrospective cohort of 108 recipients of wedge resection and 187 recipients of lobectomy for stage I/0 lung adenocarcinomas ≤2.0 cm was assembled from 2 institutions. All tumors were classified by a single pathologist, and interobserver reproducibility was assessed in a subset (n = 92) by 5 pathologists. Results: Angioinvasive adenocarcinoma (21%-27% of cases) was associated with worse outcomes when treated with wedge resection compared to lobectomy (5-year recurrence-free survival, 57% vs 85% [P = .007]; 5-year disease-free survival [DSS], 70% vs 90% [P = .043]; 7-year overall survival, 37% vs 58% [P = .143]). Adenocarcinoma in situ (AIS), minimally invasive adenocarcinoma (MIA), and LMP exhibited 100% 5-year DSS regardless of the surgical approach. Multivariable analysis showed that angioinvasion, tumor size, margin status, and extent of nodal sampling were significantly associated with recurrence but not with surgical procedure. There was substantial interobserver reproducibility among the pathologists for the diagnosis of angioinvasive adenocarcinoma (κ = 0.71) and the combined indolent AIS/MIA/LMP group (κ = 0.74). Conclusions: The majority (∼75%) of lung adenocarcinomas ≤2 cm are adequately managed with wedge resection; however, angioinvasive adenocarcinomas (∼25%) treated by wedge resection with suboptimal nodal sampling exhibit poor outcomes, with a 40% to 45% rate of recurrence within 5 years and 60% to 65% overall mortality at 7 years.

Synthesis, characterization, anti-mycobacterial activity and in silico study of new 2,5-disubstituted-1,3,4-oxadiazole derivatives.

A series of new 2,5-disubstituted-1,3,4-oxadiazole derivatives (5a-j and 6a-j) have been designed and synthesized in four-steps. Sixteen compounds among the twenty compounds are reported for the first time. The compounds were characterized and confirmed by the FTIR, 1D- and 2D-NMR and HRMS analyses, and were tested against Mycobacterium smegmatis and Mycobacterium tuberculosis H37Ra. Compound 5d was the most active against M. smegmatis with MIC value of 25 µM, and exhibited cidal activity with MBC of 68 µM, respectively. The time-kill assay showed the good killing rate at 77% with the combination of isoniazid (INH). In addition, checkboard assay confirmed the interaction of compound 5d was categorised as additive. Docking simulation has been performed to position 5d into the pantothenate synthetase active site with binding free energy value -8.6 kcal mol-1. It also occupied the same active site as that of standard native ligand with similar interactions, which clearly indicate their potential as pantothenate synthetase inhibitor.

Synthesis, characterization, anti-mycobacterial activity and in silico study of new 2,5-disubstituted-1,3,4-oxadiazole derivatives

@#A series of new 2,5-disubstituted-1,3,4-oxadiazole derivatives (5a-j and 6a-j) have been designed and synthesized in four-steps. Sixteen compounds among the twenty compounds are reported for the first time. The compounds were characterized and confirmed by the FTIR, 1D- and 2D-NMR and HRMS analyses, and were tested against Mycobacterium smegmatis and Mycobacterium tuberculosis H37Ra. Compound 5d was the most active against M. smegmatis with MIC value of 25 µM, and exhibited cidal activity with MBC of 68 µM, respectively. The time-kill assay showed the good killing rate at 77% with the combination of isoniazid (INH). In addition, checkboard assay confirmed the interaction of compound 5d was categorised as additive. Docking simulation has been performed to position 5d into the pantothenate synthetase active site with binding free energy value –8.6 kcal mol-1. It also occupied the same active site as that of standard native ligand with similar interactions, which clearly indicate their potential as pantothenate synthetase inhibitor.

Not Just for Dancing? A Content Analysis of Concussion and Head Injury Videos on TikTok.

Social media platforms are an accessible and increasingly used way for the public to gather healthcare-related information, including on sports injuries. "TikTok" is currently one of the fastest-growing social media platforms worldwide, and it is especially popular amongst adolescents and young adults. The widespread use and popularity of TikTok suggests that this platform has potential to be a source for healthcare information for younger individuals. The aim of this study was to gain a preliminary understanding of the concussion/head injury-related information on TikTok, and to gauge if TikTok could serve as a platform for concussion education. This exploratory study used a systematic search strategy to understand more about how concussion is being portrayed through TikTok videos. Using the keywords "concussion" and "head injury," 200 videos were downloaded from TikTok and 43 videos were excluded. Of the 92 videos retrieved using the keyword "concussion," 95% (n = 88) had more than 100,000 views and 6% (n = 10) had been viewed more than 10 million times. Over half, 54% (n = 50) of the "concussion" videos depicted individuals "playing around" and getting hit in the head, whilst only 1% (n = 1) of the TikTok videos were categorized as "explaining concussion facts." The large numbers of views of concussion-related TikTok videos demonstrates the popularity of this platform and indicates that healthcare organizations should consider TikTok as a potential means for concussion education amongst younger individuals.

Endoscopic balloon dilatation of the olfactory cleft - a feasibility study of a novel technique in cadavers.

OBJECTIVE: Smell dysfunctions are common with almost 20% percent of the population affected. There are no interventional solutions for these patients. The aim of this study is to investigate the feasibility and security of the balloon dilatation technique. METHODS: This paper describes interventional steps and determines the feasibility and safety of endoscopic olfactory cleft dilatation via balloon device. We included 10 nasal cavities in the study and dilated olfactory cleft areas via balloon device. RESULTS: We could smoothly perform the procedure and did not observe any fractures on the skull base or olfactory cleft of the cadavers after dilatation. CONCLUSIONS: A combination of this intervention with medical treatments can be promising for smell dysfunctions.

Noninvasive Follicular Thyroid Neoplasm with Papillary-Like Nuclear Features: Epidemiology and Long-Term Outcomes in a Strictly Defined Cohort.

Background: A subset of encapsulated/circumscribed follicular variant of papillary thyroid carcinoma (FVPTC) was reclassified as noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) in 2016 to reduce overtreatment of a low-risk tumor. Study objectives were to describe the epidemiology and long-term outcomes of NIFTP in a high-volume, urban, tertiary referral center. Methods: Among patients enrolled in the Boston Medical Center (BMC) Thyroid Cancer Registry, 110 cases of FVPTC underwent index thyroid surgery at BMC between 2000 and 2016. Historically, BMC pathologists assess all malignant nodules using sections ≤0.3 cm with evaluation of the entire nodule and capsule. After review of pathology reports to identify potential NIFTPs, slides were rereviewed using criteria established by the NIFTP Working Group in 2016 and 2018. We evaluated interobserver reliability using Cohen's Kappa coefficient. Results: Among 110 FVPTCs, 15 (13%) met NIFTP criteria; 11 women and 4 men, age range 31-64 (mean 47.5) years. Mean tumor diameter was 1.7 cm (compared with 2.2 cm for FVPTC). Among NIFTP cases, there were no lymph node metastases, distant metastases, or tumor recurrences. All NIFTP cases were American Thyroid Association (ATA) low risk compared with only 68% of FVPTC (p = 0.011). Among FVPTCs, 14% had positive lymph nodes at index operation. Four patients (4%) had distant metastases. Mean follow-up time was 46 and 69 months for FVPTC and NIFTP, respectively. Among FVPTCs with an excellent response to therapy (2015 ATA guidelines), there were no recurrences. Just over half (n = 8) of patients with NIFTP received postoperative radioactive iodine (RAI) therapy. Concordance between pathologists was high for ruling out NIFTP (75%), but only 36% for ruling in NIFTP. Overall, for NIFTP designation, Cohen's Kappa was 0.39, which is considered fair. Conclusions: Although this is a relatively small cohort, all NIFTP specimens underwent updated pathology review consistent with current guidelines; mean follow-up was nearly 6 years. NIFTP represents a small fraction of the total papillary neoplasia diagnosed at this tertiary referral center (2.3%). None of the NIFTP cohort experienced an adverse oncologic event, and there were no regional or distant metastases. Over 50% of patients with NIFTP received RAI. Thus, the NIFTP reclassification may substantially reduce the number of patients who require adjuvant therapies, such as completion surgery or RAI.

A Comparison between Mygind and Kaiteki positions in administration of drops to the olfactory cleft.

OBJECTIVES: Topical nasal steroids are a common treatment intervention for olfactory dysfunction. Penetration of topical treatment to the olfactory cleft (OC), such as nasal drops, is greatly dependent on the position of the head when the treatment is administered. We aimed to examine the penetrance of nasal drops to the OC in two different head positions: the Mygind (lying head back) position and the Kaiteki position. DESIGN AND SETTING: The specimens were firstly positioned in Mygind, and thereafter in Kaiteki positions. Nasal drops mixed with blue food dye were administered into the nostrils in each of the head position. Endoscopic videos were recorded, and two blinded observers scored the extent of olfactory cleft penetration (OCP) using a 4-point scale (0 = none, 3 = heavy). PARTICIPANTS: Twelve fresh-frozen cadaver specimens. MAIN OUTCOME MEASURES: Penetration of the dye into the OC. RESULTS: The mean score of nasal drops penetrance to the OC in the Mygind position was 1.34 (standard deviation, SD = 0.92), as compared to 1.76 (SD = 0.65) in the Kaiteki position. The difference in the OCP score between the two groups was not statistically significant (P > .05). CONCLUSION: Both Mygind and Kaiteki head positions are reasonable options for patients considering topical nasal drops for olfaction impairment. The preference of one position over the other should be determined by patient's preference and comfort.

Pulmonary Adenocarcinomas of Low Malignant Potential: Proposed Criteria to Expand the Spectrum Beyond Adenocarcinoma In Situ and Minimally Invasive Adenocarcinoma.

Lung cancer screening has improved mortality among high-risk smokers but has coincidentally detected a fraction of nonprogressive adenocarcinoma historically classified as bronchoalveolar carcinoma (BAC). In the National Lung Screening Trial (NLST) the majority of BAC-comprising 29% of computed tomography-detected stage I lung adenocarcinoma-were considered overdiagnosis after extended follow-up comparison with the control arm. In the current classification, adenocarcinoma in situ and minimally invasive adenocarcinoma have replaced BAC but together comprise only ∼5% of stage I lung adenocarcinoma. Lepidic and subsets of papillary and acinar adenocarcinoma also infrequently recur. We, therefore, propose criteria for low malignant potential (LMP) adenocarcinoma among nonmucinous adenocarcinoma measuring ≤3 cm in total, exhibiting ≥15% lepidic growth, and lacking nonpredominant high-grade patterns (≥10% cribriform, ≥5% micropapillary, ≥5% solid), >1 mitosis per 2 mm2, angiolymphatic or visceral pleural invasion, spread through air spaces or necrosis. We tested these criteria in a multi-institutional cohort of 328 invasive stage I (eighth edition) and in situ adenocarcinomas and observed 16% LMP and 7% adenocarcinoma in situ/minimally invasive adenocarcinoma which together (23%) approximated the frequency of overdiagnosed stage I BAC in the NLST. The LMP group had 100% disease-specific survival. The proposed LMP criteria, incorporating multiple histologic parameters, may be a clinically useful "low-grade" prognostic group. Validation of these criteria in additional retrospective cohorts and prospective screen-detected cohorts should be considered.

Six-year experience of detection and investigation of possible Middle East Respiratory Syndrome coronavirus cases, England, 2012-2018.

OBJECTIVES: Surveillance for Middle East Respiratory Syndrome (MERS) has been undertaken in the UK since September 2012. This study describes the surveillance outcomes in England from 2012 to 2018. STUDY DESIGN: This was a descriptive study using surveillance data. METHODS: Local health protection teams in England report possible MERS cases to the National Infection Service with clinical and laboratory data. RESULTS: A total of 1301 possible MERS cases were identified in the study period. Five cases were laboratory-confirmed MERS. The majority of cases had travelled to Saudi Arabia (56.7%) and United Arab Emirates (25.9%). Fifty-four percent of cases were men and 43.7% were women. The majority of cases (65.1%) were aged 45 years or older. The number of tests increased in the period after Hajj each year. Laboratory-confirmed alternative diagnoses were available for 513 (39.4%) cases; influenza was the most common virus detected (n = 255, 52.4%). CONCLUSIONS: Our study highlights the importance of differential diagnosis of influenza and other respiratory pathogens and early influenza antiviral treatment.

Qualitative risk assessment of follicle stimulating hormone injectable products.

BACKGROUND: Gonadotropin injections for fertility treatment regimens are usually self-injected, typically over 8-12 days during the assisted reproductive technology cycle. Parenteral gonadotropins are available in different formulations and administered through various systems. A user experience study and risk assessment were performed to evaluate different product types for risks to the patient when preparing and administering injections. METHODS: Nine women of child-bearing age each prepared and administered injections of six products representing single- and multidose vials of menotropin for reconstitution (Merional® and Menopur®), follicle stimulating hormone (FSH) reusable pen injectors with (Puregon®), and without cartridges (Gonal-f®), and single-use FSH pre-filled pens (Bemfola®). Risk assessments based on user feedback were made with reference to EU regulations for implementing practices for safe use of injectable products. RESULTS: Products requiring reconstitution with diluent in glass ampoules were associated with medium risk for sharps injury and a lower level of user confidence. Pen injectors were considered easy-to-use, with a low risk of sharps injury. Single-use pens were associated with the lowest risk of dosing errors. CONCLUSIONS: The study identifies differences in the risks for both sharps injuries and dosing errors between FSH delivery options that practitioners should consider when making a treatment choice.

'Sometimes you are forced to play God ': a qualitative study of healthcare worker experiences of using continuous positive airway pressure in newborn care in Kenya.

​OBJECTIVE: To explore the experiences of using continuous positive airway pressure (CPAP) in newborn care among healthcare workers in Kenya, and to identify factors that would promote successful scale-up. ​DESIGN AND SETTING: A qualitative study using key informant interviews and focus group discussions, based at secondary and tertiary level hospitals in Kenya. ​PARTICIPANTS: Healthcare workers in the newborn units providing CPAP. ​PRIMARY AND SECONDARY OUTCOME MEASURE: Facilitators and barriers of CPAP use in newborn care in Kenya. ​RESULTS: 16 key informant interviews and 15 focus group discussions were conducted across 19 hospitals from September 2017 to February 2018. Main barriers reported were: (1) inadequate infrastructure to support the effective delivery of CPAP, (2) shortage of skilled staff rendering it difficult for the available staff to initiate or monitor infants on CPAP and (3) inadequate knowledge and training of staff that inhibited the safe care of infants on CPAP. Key facilitators reported were positive patient outcomes after CPAP use that increased staff confidence and partnership with caregivers in the management of newborns on CPAP. Healthcare workers in private/mission hospitals had more positive experiences of using CPAP in newborn care as the relevant support and infrastructure were available. ​CONCLUSION: CPAP use in newborn care is valued by healthcare workers in Kenya. However, we identified key challenges that threaten its safe use and sustainability. Further scale-up of CPAP in newborn care should ensure that staff members have ready access to optimal training on CPAP and that there are enough resources and infrastructure to support its use. ETHICS: This study was approved through the appropriate ethics committees in Kenya and the UK (see in text) with written informed consent for each participant.

Readability of Information on Smartphone Apps for Total Hip Replacement and Total Knee Replacement Surgery Patients.

BACKGROUND: Readability is a vital component of health information and providing this material at an appropriate literacy level may positively influence patient experience. OBJECTIVE: To assess the readability of the information provided within total hip replacement and total knee replacement apps to understand more about the impact this could have on patients. METHOD: A systematic search was conducted across the 5 most popular smartphone app stores: iTunes, Google Play, Windows Mobile, Blackberry App World, and Nokia Ovi. Apps were identified for screening if they: targeted total hip replacement or total knee replacement patients; were free of charge; and were in English. App readability assessment was conducted independently by 3 reviewers using the Gunning Fog Index, the Flesch Reading Ease Score, and the Flesch-Kincaid Grade Level. RESULTS: Fifteen apps met the inclusion criteria. Only one app was found "easy to read" (My THR). CONCLUSION: Findings suggest that the overall readability of information provided is written at a level which is difficult for patients to comprehend. App developers should engage patients in the design process of their apps, in order to enhance patient experience and for the potential impact of these innovative health technologies to be truly realized.