Highly sensitive tandem mass spectrometric measurement of serum estradiol without derivatization and pediatric reference intervals in children and adolescents.

OBJECTIVES: Monitoring estradiol (E2) is important for determining the onset of pubertal development as well as in the evaluation of girls with precocious puberty. However, E2 measurement remains an analytical challenge in children, who have lower circulating levels. We developed and evaluated a simple and sensitive LC-MS/MS procedure for serum E2 quantification in pediatric populations and established age- and sex-specific pediatric reference intervals. METHODS: Residual patient serum samples were used to evaluate the analytical performance of our in-house LC-MS/MS E2 assay. The evaluation included accuracy, precision, linearity, functional sensitivity (LLoQ), and method comparison. Age- and sex-specific pediatric E2 reference intervals were also established from a cohort of 405 healthy children (birth to 18 years) recruited with informed consent. Age- and sex-specific differences were assessed, and outliers were removed. Reference intervals were established using the robust method. RESULTS: The assay imprecision was <5.3 %. Assay linearity ranged from 13.7 to 1923.3 pmol/L. The LLoQ corresponding to a CV of 20 % was determined to be 8.9 pmol/L. Bland-Altman analysis revealed a mean bias of 29.3 pmol/L or 9.1 % between our LC-MS/MS E2 assay and an external reference laboratory measuring E2 by LC-MS/MS. CONCLUSIONS: Our LC-MS/MS E2 assay shows acceptable accuracy, precision, functional sensitivity (LLoQ), and linearity for E2 quantification. Our LC-MS/MS E2 assay also showed good agreement with an external reference laboratory measuring E2 by LC-MS/MS. In addition, using CALIPER samples, we established robust age- and sex-specific pediatric E2 reference intervals to improve accuracy of test result interpretation and clinical decision making.

Language acquisition in a multilingual society: English vocabulary norms and predictors in Singaporean children.

In this study, infant vocabulary development was tracked in a multilingual society (Singapore) within a socioeconomically diverse sample. The sample comprised 1316 infants from 17.4 to 27.7 months (669 females, 647 males; 88% Chinese race, 4% Malay, 4% Indian, and 0.004% mixed-race [4% declined to provide race information]). Children varied in English language exposure and socioeconomic status. Analyses focused on identifying demographic predictors of English vocabulary size in multilingually exposed infants. Adaptations of the Macarthur-Bates Communicative Development Inventory for English, Mandarin, and Malay are provided as well as English vocabulary norms that account for variation in English exposure. This manuscript reports the first set of English language norms-calibrated to English exposure-for multilingual infants in a non-Western setting.

Infants recognize words spoken through opaque masks but not through clear masks.

COVID-19 has modified numerous aspects of children's social environments. Many children are now spoken to through a mask. There is little empirical evidence attesting to the effects of masked language input on language processing. In addition, not much is known about the effects of clear masks (i.e., transparent face shields) versus opaque masks on language comprehension in children. In the current study, 2-year-old infants were tested on their ability to recognize familiar spoken words in three conditions: words presented with no mask, words presented through a clear mask, and words presented through an opaque mask. Infants were able to recognize familiar words presented without a mask and when hearing words through opaque masks, but not when hearing words through clear masks. Findings suggest that the ability of infants to recover spoken language input through masks varies depending on the surface properties of the mask.

Heart Rate Measures From Wrist-Worn Activity Trackers in a Laboratory and Free-Living Setting: Validation Study.

BACKGROUND: Wrist-worn activity trackers are popular, and an increasing number of these devices are equipped with heart rate (HR) measurement capabilities. However, the validity of HR data obtained from such trackers has not been thoroughly assessed outside the laboratory setting. OBJECTIVE: This study aimed to investigate the validity of HR measures of a high-cost consumer-based tracker (Polar A370) and a low-cost tracker (Tempo HR) in the laboratory and free-living settings. METHODS: Participants underwent a laboratory-based cycling protocol while wearing the two trackers and the chest-strapped Polar H10, which acted as criterion. Participants also wore the devices throughout the waking hours of the following day during which they were required to conduct at least one 10-min bout of moderate-to-vigorous physical activity (MVPA) to ensure variability in the HR signal. We extracted 10-second values from all devices and time-matched HR data from the trackers with those from the Polar H10. We calculated intraclass correlation coefficients (ICCs), mean absolute errors, and mean absolute percentage errors (MAPEs) between the criterion and the trackers. We constructed decile plots that compared HR data from Tempo HR and Polar A370 with criterion measures across intensity deciles. We investigated how many HR data points within the MVPA zone (≥64% of maximum HR) were detected by the trackers. RESULTS: Of the 57 people screened, 55 joined the study (mean age 30.5 [SD 9.8] years). Tempo HR showed moderate agreement and large errors (laboratory: ICC 0.51 and MAPE 13.00%; free-living: ICC 0.71 and MAPE 10.20%). Polar A370 showed moderate-to-strong agreement and small errors (laboratory: ICC 0.73 and MAPE 6.40%; free-living: ICC 0.83 and MAPE 7.10%). Decile plots indicated increasing differences between Tempo HR and the criterion as HRs increased. Such trend was less pronounced when considering the Polar A370 HR data. Tempo HR identified 62.13% (1872/3013) and 54.27% (5717/10,535) of all MVPA time points in the laboratory phase and free-living phase, respectively. Polar A370 detected 81.09% (2273/2803) and 83.55% (9323/11,158) of all MVPA time points in the laboratory phase and free-living phase, respectively. CONCLUSIONS: HR data from the examined wrist-worn trackers were reasonably accurate in both the settings, with the Polar A370 showing stronger agreement with the Polar H10 and smaller errors. Inaccuracies increased with increasing HRs; this was pronounced for Tempo HR.

Assessment of occupational exposure to airborne chlorine dioxide of healthcare workers using impregnated wipes during high-level disinfection of non-lumened flexible nasoendoscopes.

Routine flexible nasoendoscopy in otolaryngology clinics is well established, the rate-limiting step of which being the speed of the nasoendoscopes reprocessing method used. Non-lumened flexible nasoendoscopes are expensive, heat-sensitive, delicate instruments that cannot be sterilized in an autoclave but must be disinfected by means of high level disinfection (HLD). In one of the public hospitals in Singapore, the method of disinfection was recently changed to the use of commercial impregnated wipes which generates less than 1% chlorine dioxide upon activation. An exposure assessment was performed to assess the potential exposure of healthcare workers (HCWs) to airborne chlorine dioxide during nasoendoscope disinfection. A total of 14 long-term personal samples, four short-term personal samples and 16 long-term area samples were collected over 8 days in midget impingers containing 0.02% potassium iodide in sodium carbonate/sodium bicarbonate buffer during the nasoendoscope disinfection. The samples were then analyzed by ion-chromatograph. The chlorine dioxide concentrations and upper confidence limit at 95% confidence level (UCL95%) for personal and area samples collected were all below the occupational exposure limits (OEL) for chlorine dioxide (Singapore Workplace Safety and Health PELs, ACGIH TLVs, U.S. OSHA PELs). The study presented evidence that the exposure of HCWs to chlorine dioxide during high-level disinfection of flexible nasoendoscopes were deemed insignificant.

Bar Code-Based Management to Enhance Efficiency of a Sterile Supply Unit in Singapore.

Sterile surgical instruments are essential for successful surgical outcomes. The Singapore General Hospital's Theatre Sterile Supplies Unit (TSSU) has faced many challenges, including increasing demand for instruments and the need to maintain instruments of greater complexity. To address these challenges, stakeholders from key departments at Singapore General Hospital formed a multidisciplinary team to transform operations in the TSSU. The team adopted and implemented the TSSU Instrument Management System (TIMS) in three phases over five years. The project included standardizing instrument-naming conventions, implementing electronic integration of instrument tracking in the unit, extending traceability of instruments to the major ORs, initiating integrated web-based instrument ordering, and extending the system management of instruments at ambulatory surgery and specialized OR facilities. The implementation of TIMS has improved inventory, supply, and quality management; reduced instrument repairs; and led to savings through increased productivity and lower expenses.

Diagnostic criteria of carpal tunnel syndrome using high-resolution ultrasonography: correlation with nerve conduction studies.

The aim of this work was to evaluate the diagnostic performance of grey-scale, color Doppler, and dynamic ultrasound (US) for diagnosing carpal tunnel syndrome (CTS) using the medical diagnostic test called nerve conduction study (NCS) as the reference standard, and to correlate the increase in median nerve (MN) cross-sectional area (CSA) with severity of CTS. Fifty-one patients (95 wrists) with clinical symptoms of idiopathic CTS were recruited. The CSA and flattening ratio of the MN were measured at the distal radio-ulnar joint, pisiform, and hamate levels; bowing of the flexor retinaculum was determined at the hamate level. The hypervascularity of the MN was evaluated. The transverse sliding of the MN was observed dynamically and recorded as being either normal or restricted/absent. Another 15 healthy volunteers (30 wrists) were recruited as controls. Interoperator reliability was established for all criteria. CTS was confirmed in 75 wrists (75/95: 79%; 14 minimal, 21 mild, 23 moderate, 17 severe). CSA at the pisiform level was found to be the most reliable and accurate grey-scale criterion to diagnose CTS (optimum threshold: 9.8 mm(2)). There was a good correlation between the severity of NCS and CSA (r = 0.78, p < 0.001). The sensitivity and specificity of color-Doppler and dynamic US in detecting CTS was 69, 95, 58, and 86%, respectively. Combination of these subjective criteria with CSA increases the sensitivity to 98.3%. US measurement of CSA provides additional information about the severity of MN involvement. Color-Doppler and dynamic US are useful supporting criteria that may expand the utility of US as a screening tool for CTS.

Epidemiology of hand infection--a comparative study between year 2000 and 2009.

This study aims to analyze the bacteriology and antibiotic resistance in hand infection between 2000 and 2009 at a local hospital in Asia. It is a retrospective study involving all adult patients with hand infections that were treated surgically, with tissue or wound culture sent. A total of 100 cases in 2000 and 98 cases in 2009 were included in this study. Standard epidemiology information, bacteriology, antibiotic sensitivity and treatment outcome were analyzed. Particular interest was given to diabetic hand infection. There was no significant difference of outcome in hand infection between the two years. The outcome of diabetics was not statistically worse than the non-diabetics. Comparing the patients in 2000 and 2009, more younger patients were affected with hand infection in 2009. While length of stay is shorter in 2009. Mixed infection was more common in diabetics in 2009. There was trend of clindamycin resistance in methicillin-sensitive staphylococcus aureus in 2009.

Outcomes of open carpal tunnel releases and its predictors: a prospective study.

A prospective study of 74 patients who underwent open carpal tunnel releases was conducted, with a follow-up period of six months. We analyzed multiple preoperative variables in order to identify factors that might predict outcomes. These outcomes included improvement in symptom severity and functional severity scores, grip strength as well as patient satisfaction. All the patients showed improvement in symptoms with 72% showing complete symptomatic relief, 74% showing improvement in function and 66% showing improvement in grip strength, and 82% were either completely or very satisfied with the results of surgery. Older patients and patients with weakness were associated with poorer outcomes. Higher preoperative symptom severity and functional severity scores were also associated with less improvement in symptoms and function, respectively. This information would benefit the surgeons and patients during preoperative counseling and help facilitate the decision-making process for both parties.

A multistate outbreak of hepatitis A associated with semidried tomatoes in Australia, 2009.

BACKGROUND: A large outbreak of hepatitis A affected individuals in several Australian states in 2009, resulting in a 2-fold increase in cases reported to state health departments compared with 2008. Two peaks of infection occurred (April-May and September-November), with surveillance data suggesting locally acquired infections from a widely distributed food product. METHODS: Two case-control studies were completed. Intensive product trace-back and food sampling was undertaken. Genotyping was conducted on virus isolates from patient serum and food samples. Control measures included prophylaxis for close contacts, public health warnings, an order by the chief health officer under the Victorian Food Act 1984, and trade-level recalls on implicated batches of semidried tomatoes. RESULTS: A multijurisdictional case-control study in April-May found an association between illness and consumption of semidried tomatoes (odds ratio [OR], 3.0; 95% CI 1.4-6.7). A second case-control study conducted in Victoria in October-November also implicated semidried tomatoes as being associated with illness (OR, 10.3; 95% CI, 4.7-22.7). Hepatitis A RNA was detected in 22 samples of semidried tomatoes. Hepatitis A virus genotype IB was identified in 144 of 153 (94%) patients tested from 2009, and partial sequence analysis showed complete identity with an isolate found in a sample of semidried tomatoes. CONCLUSIONS: The results of both case-control studies and food testing implicated the novel vehicle of semidried tomatoes as the cause of this hepatitis A outbreak. The outbreak was extensive and sustained despite public health interventions, the design and implementation of which were complicated by limitations in food testing capability and complex supply chains.

Mycobacterium abscessus Hand Infections in Immunocompetent Fish Handlers: Case Report.

Mycobacterium abscessus hand infections are rare and usually occur in immunocompromised patients or after injection with contaminated injectables. This article describes 2 cases of M abscessus infection of the hand in otherwise healthy fish handlers. Mycobacterium abscessus can cause severe chronic tenosynovitis even in immunocompetent patients and should be suspected alongside the more common M marinum as a cause of nontuberculous mycobacterial hand infections in patients with aquatic and fish exposure.

Pincer nails complicated by distal phalangeal osteomyelitis.

SUMMARY: Besides the known cosmetic implications, pincer nails are often complicated by pain, chronic inflammation and recurrent suppurative infections. We report two such cases of chronic paronychia of the thumb secondary to pincer nails. Both were complicated by osteomyelitis. Although both cases eventually healed after excisional debridement, one case required elective amputation because the significant loss of bony support resulted in a painful, floppy fingertip and poor pinch. Regular radiographic assessments may be useful in the management of patients with chronic inflammation or recurrent paronychias secondary to pincer nails to detect osteomyelitis.

Approach to debridement in necrotizing fasciitis.

Aggressive debridement is a cornerstone intervention in necrotizing fasciitis. Our approach consists of 4 steps: (1) confirming the diagnosis and isolate the causative organism; (2) defining the extent of fasciitis; (3) surgical excision; and (4) post-excision wound care. The extent of the infection is defined by probing the wound bluntly. Systematic excision follows. Fascial excision must be complete and uncompromising with the full extent of the involved wound laid open. We classify the infected skin into zones 1, 2, and 3. Zone 1 is necrotic tissue. Zone 2 is infected but potentially salvageable soft tissue, and zone 3 is non-infected skin. Zone 1 is completely excised. Zone 2 is meticulously assessed and cut back as necessary to remove nonviable tissue while maximally preserving salvageable tissue. Zone 3 is left alone. The aim of surgical debridement is to remove all infected tissue in a single operation. This halts the progression of the fasciitis and minimizes unnecessary returns to the operating room.

Synovial cell culture and tissue engineering of a tendon synovial cell biomembrane.

Restrictive adhesions are a common complication of tendon injury and repair in the hand, resulting in severe dysfunction. Creating a barrier between the repair sites and surrounding tissue layers may prevent adhesions. We present the first stage in the process of developing a synovial biomembrane for this purpose. Synovial cells harvested from the Achilles tendon sheath and the knee joint of a Wistar albino rat were cultured for 2 weeks in culture medium, and then impregnated into a collagen type 1 matrix for another 2 weeks. Cells originating from both tendon and synovium demonstrated cell growth and layer formation on the surfaces of the matrix 2 weeks after impregnation. Alcian blue staining using Scott's method demonstrated the presence of acidic mucopolysaccharide, indicating hyaluronic acid (HA) production. This provides indirect evidence of functioning synovial cells on the membrane. It is possible to culture synovial cells and engineer a synoviocyte-collagen membrane that synthesizes endogenous HA. Application of this biomembrane to tendon repair sites may help to prevent adhesions after tendon repairs. Evaluation of this method on in vivo models is required.

Factors affecting the prognosis of pyogenic flexor tenosynovitis.

BACKGROUND: Pyogenic flexor tenosynovitis is a closed space infection involving the digital flexor tendon sheaths of the upper extremity that can cause considerable morbidity. The purpose of the present report is to describe the various risk factors leading to poor outcomes and to recommend a clinical classification system for this condition. METHODS: We studied seventy-five patients with pyogenic flexor tenosynovitis over a six-year period. The amputation rate and total active motion were used as outcomes measures. The clinical factors influencing outcomes were identified and analyzed. RESULTS: The five risk factors associated with poor outcomes were (1) an age of more than forty-three years, (2) the presence of diabetes mellitus, peripheral vascular disease, or renal failure, (3) the presence of subcutaneous purulence, (4) digital ischemia, and (5) polymicrobial infection. On the basis of the clinical findings and outcomes, three distinct groups of patients could be identified, each with a progressively worse outcome. Patients in Group I had no subcutaneous purulence or digital ischemia; these patients had the best prognosis, with no amputations and a mean 80% return of total active motion. Patients in Group II demonstrated the presence of subcutaneous purulence but no ischemic changes; these patients had an amputation rate of 8% and a mean 72% recovery of total active motion. Patients in Group III had both extensive subcutaneous purulence and ischemic changes; these patients had the worst prognosis, with an amputation rate of 59% and a mean 49% return of total active motion. CONCLUSIONS: We propose a three-tier clinical classification system that can aid in prognosis and guidance in the treatment of pyogenic flexor tenosynovitis of the upper extremity.

Mycobacterium marinum as a cause of chronic granulomatous tenosynovitis in the hand.

OBJECTIVE: Mycobacterium marinum is an uncommon cause of chronic granulomatous flexor tenosynovitis and leads to significant morbidity in the hand. This paper aims to review our treatment of this infection and its clinical outcomes. METHODS: We treated five cases of M. marinum flexor tenosynovitis from 2001 to 2006, which were confirmed after 6 weeks of mycobacterial culture. RESULTS: All the patients were healthy immuno-competent hosts. There was a history of injury by a marine animal in each patient. Presentation was delayed at an average of 32.0 days after the injury. Excisional debridement was performed at an average of 63.4 days after the injury. The average number of debridements performed was 3.4. One patient had to undergo ray amputation to control the infection. The average duration of oral antibiotics was 15.4 weeks. Post-operatively, there were reductions in total active motion in all patients. CONCLUSION: A high index of suspicion, based on the history and intra-operative findings, is necessary when managing these patients. This infection runs a protracted course that requires multiple debridements and is associated with poor functional outcome.

Necrotising fasciitis and traditional medical therapy-- a dangerous liaison.

INTRODUCTION: Necrotising fasciitis is a disease associated with high morbidity and mortality, and multi-focal necrotising fasciitis is uncommon. We present 2 cases of concurrent necrotising fasciitis of contralateral upper and lower limbs. CLINICAL PICTURE: Both presented with pain, swelling, bruising or necrosis of the affected extremities. Traditional medical therapy was sought prior to their presentation. TREATMENT: After initial debridement, one patient subsequently underwent amputation of the contralateral forearm and leg. The other underwent a forearm amputation, but refused a below-knee amputation. OUTCOME: The first patient survived, while the second died. CONCLUSION: Traditional medical therapy can cause bacterial inoculation, leading to necrotising fasciitis, and also leads to delay in appropriate treatment. Radical surgery is needed to optimise patient survival.

Salmonella surveillance in Australia--created from adversity.

A national scheme of Salmonella surveillance emerged in Australia as a direct result of high-profile outbreaks in 1977. A typing laboratory in Victoria put together a working model using the computer technology available at the time. The evolving information-gathering system has stood the test of time and has provided an invaluable bank of information covering isolations from humans and other sources. The databases have been used effectively in detecting trends and outbreaks and have assisted in the solution of public health problems--even extending internationally. The way in which this has been done and the lessons learned are described.

The structure of gelsolin bound to ATP.

Calcium activation of the actin-modifying properties of gelsolin is sensitive to ATP. Here, we show that soaking calcium-free gelsolin crystals in ATP-containing media results in ATP occupying a site that spans the two pseudosymmetrical halves of the protein. ATP binding involves numerous polar and hydrophobic contacts and is identical for the two copies of gelsolin related by non-crystallographic symmetry within the crystal. The gamma-phosphate of ATP participates in several charge-charge interactions consistent with the preference of gelsolin for ATP, as a binding partner, over ADP. In addition, disruption of the ATP-binding site through Ca2+ activation of gelsolin reveals why ATP binds more tightly to the inactive molecule, and suggests how the binding of ATP may modulate the sensitivity of gelsolin to calcium ions. Similarities between the ATP and PIP2 interactions with the C-terminal half of gelsolin are evident from their overlapping binding sites and in that both molecules bind more tightly in the absence of calcium ions. We propose a model for how PIP2 may bind to calcium-free gelsolin based on the ATP-binding site.