Mapping internal temperatures during high-rate battery applications.

Electric vehicles demand high charge and discharge rates creating potentially dangerous temperature rises. Lithium-ion cells are sealed during their manufacture, making internal temperatures challenging to probe1. Tracking current collector expansion using X-ray diffraction (XRD) permits non-destructive internal temperature measurements2; however, cylindrical cells are known to experience complex internal strain3,4. Here, we characterize the state of charge, mechanical strain and temperature within lithium-ion 18650 cells operated at high rates (above 3C) by means of two advanced synchrotron XRD methods: first, as entire cross-sectional temperature maps during open-circuit cooling and second, single-point temperatures during charge-discharge cycling. We observed that a 20-minute discharge on an energy-optimized cell (3.5 Ah) resulted in internal temperatures above 70 °C, whereas a faster 12-minute discharge on a power-optimized cell (1.5 Ah) resulted in substantially lower temperatures (below 50 °C). However, when comparing the two cells under the same electrical current, the peak temperatures were similar, for example, a 6 A discharge resulted in 40 °C peak temperatures for both cell types. We observe that the operando temperature rise is due to heat accumulation, strongly influenced by the charging protocol, for example, constant current and/or constant voltage; mechanisms that worsen with cycling because degradation increases the cell resistance. Design mitigations for temperature-related battery issues should now be explored using this new methodology to provide opportunities for improved thermal management during high-rate electric vehicle applications.

Interventional management of hyperhidrosis in secondary care: a systematic review.

BACKGROUND: Hyperhidrosis is uncontrollable excessive sweating, which occurs at rest, regardless of temperature. The symptoms of hyperhidrosis can significantly affect quality of life. OBJECTIVES: To undertake a systematic review of the clinical effectiveness and safety of treatments available in secondary care for the management of primary hyperhidrosis. METHODS: Fifteen databases (including trial registers) were searched to July 2016 to identify studies of secondary-care treatments for primary hyperhidrosis. For each intervention randomized controlled trials (RCTs) were included where available; where RCT evidence was lacking, nonrandomized trials or large prospective case series were included. Outcomes of interest included disease severity, sweat rate, quality of life, patient satisfaction and adverse events. Trial quality was assessed using a modified version of the Cochrane Risk of Bias tool. Results were pooled in pairwise meta-analyses where appropriate, otherwise a narrative synthesis was presented. RESULTS: Fifty studies were included in the review: 32 RCTs, 17 nonrandomized trials and one case series. The studies varied in terms of population, intervention and methods of outcome assessment. Most studies were small, at high risk of bias and poorly reported. The interventions assessed were iontophoresis, botulinum toxin (BTX) injections, anticholinergic medications, curettage and newer energy-based technologies that damage the sweat gland. CONCLUSIONS: The evidence for the effectiveness and safety of treatments for primary hyperhidrosis is limited overall, and few firm conclusions can be drawn. However, there is moderate-quality evidence to support the use of BTX for axillary hyperhidrosis. A trial comparing BTX with iontophoresis for palmar hyperhidrosis is warranted.

High-throughput, non-invasive prenatal testing for fetal Rhesus D genotype to guide antenatal prophylaxis with anti-D immunoglobulin: a cost-effectiveness analysis.

OBJECTIVE: To evaluate the cost-effectiveness of high-throughput, non-invasive prenatal testing (HT-NIPT) for fetal Rhesus D (RhD) genotype to guide antenatal prophylaxis with anti-D immunoglobulin compared with routine antenatal anti-D immunoglobulin prophylaxis (RAADP). DESIGN: Cost-effectiveness decision-analytic modelling. SETTING: Primary care. PARTICIPANTS: A simulated population of 100 000 RhD-negative women not known to be sensitised to the RhD antigen. METHODS: A decision tree model was used to characterise the antenatal care pathway in England and the long-term consequences of sensitisation events. The diagnostic accuracy of HT-NIPT was derived from a systematic review and bivariate meta-analysis; estimates of other inputs were derived from relevant literature sources and databases. Women in whom the HT-NIPT was positive or inconclusive continued to receive RAADP, whereas women with a negative result received none. Five alternative strategies in which the use of HT-NIPT may affect the existing postpartum care pathway were considered. MAIN OUTCOME MEASURES: Costs expressed in 2015GBP and impact on health outcomes expressed in terms of quality-adjusted life-years over a lifetime. RESULTS: The results suggested that HT-NIPT appears cost saving but also less effective than current practice, irrespective of the postpartum strategy evaluated. A postpartum strategy in which inconclusive test results are distinguished from positive results performed best. HT-NIPT is only cost-effective when the overall test cost is £26.60 or less. CONCLUSIONS: HT-NIPT would reduce unnecessary treatment with routine anti-D immunoglobulin and is cost saving when compared with current practice. The extent of any savings and cost-effectiveness is sensitive to the overall test cost. TWEETABLE ABSTRACT: HT-NIPT is cost saving compared with providing anti-D to all RhD-negative pregnant women.

Systematic review of the limited evidence base for treatments of Eustachian tube dysfunction: a health technology assessment.

BACKGROUND: The Health Technology Assessment programme commissioned a wide-ranging review of treatments for adult Eustachian tube dysfunction. Treatments range from advice and observation and pharmacological treatments to surgical options. OBJECTIVE: (i) To assess the evidence for interventions for adults with a clinical diagnosis of Eustachian tube dysfunction and (ii) to identify priorities for future research. TYPE OF REVIEW: Systematic review (PROSPERO registration CRD42012003035) adhering to PRISMA guidance. SEARCH: An extensive search of 15 databases including MEDLINE, EMBASE and CENTRAL (up to October 2012). EVALUATION METHOD: Controlled and uncontrolled studies of interventions for adult Eustachian tube dysfunction were included. Because of insufficient data, the protocol was amended to also include controlled studies with mixed adult/child populations. Risk of bias was assessed. Narrative synthesis was employed due to high clinical heterogeneity. RESULTS: Interventions assessed were pharmacological treatments [two randomised controlled trials (RCTs), one controlled non-randomised trial (CCT), 159 patients]; mechanical pressure equalisation devices (one randomised controlled trial, one CCT, 48 patients); and surgery, including laser tuboplasty (seven case series, 192 patients), balloon dilatation (three case series, 103 patients), myringotomy without grommet insertion (two case series, 121 patients), transtubal steroids (one case series, 11 patients) and laser coagulation (one retrospective controlled study, 40 patients). All studies had high risk of bias except two pharmacological trials; one had low risk and one unclear risk. No evidence was found for many treatments. The single low risk of bias RCT (n = 91; 67% adults) showed no effect of nasal steroids and favoured placebo for improved middle ear function (RR 1.20, 95% CI 0.91-1.58) and symptoms (P = 0.07). Other studies showed improvements in middle ear function for mechanical devices, antihistamine/ephedrine and nasal decongestant, but they had significant methodological weaknesses including insufficient length of follow-up. None of the surgical studies were adequately controlled, and many reported high levels of co-intervention. Therefore, observed benefits for tuboplasty and balloon dilatation in symptoms, middle ear function or hearing could not be reliably attributed to the interventions assessed. There was variability in definitions of the condition. CONCLUSION: Eustachian tube dysfunction is a poorly defined condition. Due to the limited and poor-quality evidence, it is inappropriate to make conclusions on the effectiveness of any intervention; the evidence base is insufficient to guide recommendations for a trial of any particular intervention. Consensus on diagnostic criteria for Eustachian tube dysfunction is required to inform inclusion criteria of future trials.

Healthcare professionals' knowledge, understanding and confidence to manage chronic pain after cancer treatment: A UK survey.

INTRODUCTION: Healthcare professionals are vital in preparing people living with and beyond cancer about the risks of chronic pain after cancer treatment. To do so, healthcare professionals need to be knowledgeable and confident about chronic pain after cancer treatment, yet little is known about their understanding or confidence of this common long-term and late side effect of cancer treatment. AIM: To identify healthcare professionals' knowledge and understanding of chronic pain after cancer treatment and consider how confident they are to inform, listen and signpost people living with and beyond cancer to appropriate information and support. METHOD: A cross sectional online survey was distributed to healthcare professionals in the UK via cancer and primary care networks, cancer alliances and social media. The survey consisted of four domains: 1) knowledge and understanding, 2) information and support, 3) confidence and 4) barriers. Quantitative data were analysed with descriptive statistics and free text comments were analysed using qualitative content analysis. RESULTS: Healthcare professionals reported limited knowledge and understanding of chronic pain after cancer treatment. Healthcare professionals lacked confidence to talk to people about chronic pain after cancer treatment and viewed their lack of knowledge as a barrier. Additional barriers included 'Limited service provision', 'Conflict between services', 'Not my role' and 'Challenges in diagnosing chronic pain in cancer survivors'. CONCLUSION: Chronic pain after cancer can be a significant issue for those living with and beyond cancer, yet healthcare professionals report limited knowledge of it or understanding of the impact. More education is needed to increase healthcare professionals' knowledge and confidence in chronic pain after cancer treatment.

Using Middle Cerebral Artery Doppler Ultrasound to Predict Clinical Chorioamnionitis After Preterm Prelabor Rupture of Membranes.

BACKGROUND: In neonates, blood flow to the brain as measured by peak systolic velocity (PSV) in the middle cerebral artery (MCA) is altered in pregnancies affected by chorioamnionitis. OBJECTIVE: We aim to determine whether PSV and other measures of flow in the MCA in the fetus are altered prior to the development of clinical chorioamnionitis following preterm prelabor rupture of membranes (PPROM). METHODS:  This was a prospective observational study. Fifty patients from one institution were recruited after being diagnosed with PPROM between 23 weeks zero days and 33 weeks six days gestation. We performed measurements of the PSV in the fetal MCA on a weekly basis following PPROM and used the value taken closest to the time of delivery for our statistical analysis. The primary outcome assessed was clinical chorioamnionitis, and the exposure of interest was MCA PSV. Additional independent variables of interest were other Doppler measures of the MCA. Secondary outcomes included histological chorioamnionitis and other measures of neonatal health, including sepsis, days in the neonatal intensive care unit (NICU), and death. RESULTS: Of the 50 patients recruited to our study, eight (16%) developed clinical chorioamnionitis, similar to previously reported values in the general population. The PSV in the MCA was not significantly associated with the development of clinical chorioamnionitis. However, an elevated MCA pulsatility index (PI), a measure of resistance to flow, was associated with a higher probability of developing clinical chorioamnionitis. CONCLUSION:  There does not appear to be a difference in the PSV of the MCA of fetuses in pregnancies following PPROM with impending chorioamnionitis. However, elevated PI in the MCA could be a marker of impending chorioamnionitis in PPROM. Larger studies are needed to confirm these findings.

Nasopharyngeal carriage of otitis media pathogens in infants receiving 10-valent non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV10), 13-valent pneumococcal conjugate vaccine (PCV13) or a mixed primary schedule of both vaccines: A randomised controlled trial.

BACKGROUND: Aboriginal children in Northern Australia have a high burden of otitis media, driven by early and persistent nasopharyngeal carriage of otopathogens, including non-typeable Haemophilus influenzae (NTHi) and Streptococcus pneumoniae (Spn). In this context, does a combined mixed primary series of Synflorix and Prevenar13 provide better protection against nasopharyngeal carriage of NTHi and Spn serotypes 3, 6A and 19A than either vaccine alone? METHODS: Aboriginal infants (n = 425) were randomised to receive Synflorix™ (S, PHiD-CV10) or Prevenar13™ (P, PCV13) at 2, 4 and 6 months (_SSS or _PPP, respectively), or a 4-dose early mixed primary series of PHiD-CV10 at 1, 2 and 4 months and PCV13 at 6 months of age (SSSP). Nasopharyngeal swabs were collected at 1, 2, 4, 6 and 7 months of age. Swabs of ear discharge were collected from tympanic membrane perforations. FINDINGS: At the primary endpoint at 7 months of age, the proportion of nasopharyngeal (Np) swabs positive for PCV13-only serotypes 3, 6A, or 19A was 0%, 0.8%, and 1.5% in the _PPP, _SSS, and SSSP groups respectively, and NTHi 55%, 52%, and 52% respectively, and no statistically significant vaccine group differences in other otopathogens at any age. The most common serotypes (in order) were 16F, 11A, 10A, 7B, 15A, 6C, 35B, 23B, 13, and 15B, accounting for 65% of carriage. Ear discharge swabs (n = 108) were culture positive for NTHi (52%), S. aureus (32%), and pneumococcus (20%). CONCLUSIONS: Aboriginal infants experience nasopharyngeal colonisation and tympanic membrane perforations associated with NTHi, non-PCV13 pneumococcal serotypes and S. aureus in the first months of life. Nasopharyngeal carriage of pneumococcus or NTHi was not significantly reduced in the early 4-dose combined SSSP group compared to standard _PPP or _SSS schedules at any time point. Current pneumococcal conjugate vaccine formulations do not offer protection from early onset NTHi and pneumococcal colonisation in this high-risk population.

Chronic, Silent Microaspiration Masquerading as Interstitial Lung Disease.

Chronic, silent microaspiration is a common but underrecognized pathologic process in pulmonary medicine. The clinical presentation is variable and diagnosis can be challenging. We present the case of a 55-year-old woman with known emphysema, who was referred to us for progressive respiratory failure that was unresponsive to therapy. The patient had 9 hospital admissions in the preceding 5 months and was treated with multiple courses of antibiotics and systemic steroid therapy for a diagnosis of cryptogenic organizing pneumonia. The steroid therapy was complicated by 51 pounds of weight gain. She had conversational as well as profound exertional shortness of breath. Physical examination revealed a woman in moderate distress and bilateral diffuse wheezing and rhonchi. Computed tomography of the chest revealed areas of bronchocentric consolidation and bronchial wall thickening in the bilateral lower lobes. She underwent surgical lung biopsy and the histopathology was consistent with chronic aspiration pneumonia.

Rare case of parathyroid gland sarcoidosis presenting with hypercalcaemia.

Sarcoidosis of the parathyroid gland is a rare occurrence. Parathyroid sarcoidosis is usually associated with parathyroid adenomas, and, therefore, hypercalcaemia is a common presentation of this entity. We present a case of parathyroid sarcoidosis and review the world literature regarding this rare condition. A woman with a history of diffuse large B cell lymphoma underwent a surveillance positron emission tomography scan that showed increased fluorodeoxyglucose uptake in multiple thoracic and abdominal lymph nodes and in a left upper extremity soft tissue mass. Biopsy of the soft tissue mass showed non-caseating granulomas consistent with sarcoidosis. Blood work showed a serum calcium of 11.1 mg/dL with an intact serum parathyroid hormone of 92 pg/dL. Primary hyperparathyroidism was suspected. A neck ultrasound and sestamibi parathyroid scintigraphy demonstrated a parathyroid nodule. She underwent surgical resection, and the histopathology revealed a parathyroid adenoma and non-caseating granulomata consistent with a diagnosis of sarcoidosis.

Coexistent Takayasu arteritis and sarcoidosis: a case report and review of the literature.

BACKGROUND: Takayasu Arteritis (TAK) is a granulomatous large vessel vasculitis that predominantly affects the aorta, major aortic branches and pulmonary arteries resulting in pulselessness. Sarcoidosis is a systemic granulomatous disease of unknown etiology that can affect any organ. Numerous cases of coexistence of both these rare diseases have been described, suggesting that their association may be by more than chance alone. OBJECTIVE: To describe a case of coexistent TAK and sarcoidosis and review the world literature concerning this condition. METHODS: The clinical presentation and diagnostic approach is described of a woman with TAK who developed sarcoidosis. The world literature was reviewed by searching the PubMed and Google Scholar database for the terms 'Takayasu arteritis' and 'sarcoidosis'; 'Takayasu arteritis' and 'granuloma'; 'vasculitis' and 'sarcoidosis'; and 'vasculitis' and 'granuloma.' The identified individual articles were reviewed, and the bibliography of these articles were scrutinized to identify more cases. The pertinent clinical features of these cases were summarized. RESULT: A 36-year-old Caucasian woman, who was diagnosed with histologically confirmed TAK at 22 years of age, was referred for evaluation of mediastinal lymphadenopathy. The diagnosis of sarcoidosis was established on histopathology of a mediastinal lymph node biopsy. A literature review identified 23 additional cases of coexisting sarcoidosis and TAK, and the clinical features of these cases is described. CONCLUSION: TAK and sarcoidosis may occur in the same patient. Given the prevalence of these diseases, concomitant development of these two diseases is unlikely to be by chance alone and probably reflects a unifying mechanism. Clinicians should be aware of this association in patients in order to make a timely diagnosis and optimize patient care.

Are you better? A multi-centre study of patient-defined recovery from Complex Regional Pain Syndrome.

BACKGROUND: Complex Regional Pain Syndrome (CRPS) symptoms can significantly differ between patients, fluctuate over time, disappear or persist. This leads to problems in defining recovery and in evaluating the efficacy of therapeutic interventions. OBJECTIVES: To define recovery from the patients' perspective and better understand their priorities for treatment approaches. METHODS: Establishing an international consortium, we used a 2-Round Delphi-based study in eight countries across Europe and North America. Participants ≥18 years who met, or had met, Budapest clinical criteria were included. Round 1 participants completed the statement: 'I would/do consider myself recovered from CRPS if/because…' alongside demographic and health questionnaires. Data were thematically organised and represented as 62 statements, from which participants identified and ranked their recovery priorities in Round 2. RESULTS: Round 1 (N = 347, 80% female, 91% non-recovered) dominant ICF themes were: activities of daily living; bodily functions; external factors; participation and personal factors. The top five priority statements in Round 2 (N = 252) were: no longer having (1) CRPS-related pain, (2) generalised pain and discomfort, (3) restricted range of movement, (4) need for medication, (5) stiffness in the affected limb. With very few exceptions, priorities were consistent, irrespective of patient demographics/geography. Symptoms affecting daily activities were among those most frequently reported. CONCLUSIONS: Our data showed a small number of themes are of highest importance to CRPS patients' definition of recovery. Patients want their pain, movement restriction and reliance on medication to be addressed, above all other factors. These factors should therefore be foremost concerns for future treatment and rehabilitation programmes. SIGNIFICANCE: Those with longstanding CRPS may no longer meet diagnostic criteria but still be symptomatic. Defining recovery is therefore problematic in CRPS. Our study has identified patients' definition of recovery from CRPS, in order of priority, as relief from: their CRPS-related pain, generalised pain, movement restriction, reliance on medication, and stiffness.

Simple tests for the diagnosis of childhood obesity: a systematic review and meta-analysis.

There is a need to accurately quantify levels of adiposity in order to identify overweight and obesity in children. This systematic review aimed to identify all diagnostic accuracy studies evaluating simple tests for obesity and adiposity, including body mass index (BMI), skin-fold thickness and waist circumference, compared against high-quality reference tests. Twenty-four cohort studies including 25,807 children were included. BMI had good performance when diagnosing obesity: a sensitivity of 81.9% (95% confidence interval [CI]: 73.0 to 93.8) for a specificity of 96.0% (95% CI: 93.8 to 98.1). It was less effective at diagnosing overweight (sensitivity: 76.3%, 95% CI: 70.2 to 82.4; specificity: 92.1% 95% CI: 90.0 to 94.3). When diagnosing obesity, waist circumference had similar performance (sensitivity: 83.8%; specificity: 96.5%). Skin-fold thickness had slightly poorer performance (sensitivity: 72.5%; specificity: 93.7%). Few studies considered any other tests. There was no conclusive evidence that any test was generally superior to the others. BMI is a good simple diagnostic test for identifying childhood adiposity. It identifies most genuinely obese and adipose children while misclassifying only a small number as obese. There was no conclusive evidence that any test should be preferred to BMI, and the extra complexity of skin-fold thickness tests does not appear to improve diagnostic accuracy.

Childhood obesity as a predictor of morbidity in adulthood: a systematic review and meta-analysis.

Obese children are at higher risk of being obese as adults, and adult obesity is associated with an increased risk of morbidity. This systematic review and meta-analysis investigates the ability of childhood body mass index (BMI) to predict obesity-related morbidities in adulthood. Thirty-seven studies were included. High childhood BMI was associated with an increased incidence of adult diabetes (OR 1.70; 95% CI 1.30-2.22), coronary heart disease (CHD) (OR 1.20; 95% CI 1.10-1.31) and a range of cancers, but not stroke or breast cancer. The accuracy of childhood BMI when predicting any adult morbidity was low. Only 31% of future diabetes and 22% of future hypertension and CHD occurred in children aged 12 or over classified as being overweight or obese. Only 20% of all adult cancers occurred in children classified as being overweight or obese. Childhood obesity is associated with moderately increased risks of adult obesity-related morbidity, but the increase in risk is not large enough for childhood BMI to be a good predictor of the incidence of adult morbidities. This is because the majority of adult obesity-related morbidity occurs in adults who were of healthy weight in childhood. Therefore, targeting obesity reduction solely at obese or overweight children may not substantially reduce the overall burden of obesity-related disease in adulthood.

Predicting adult obesity from childhood obesity: a systematic review and meta-analysis.

A systematic review and meta-analysis was performed to investigate the ability of simple measures of childhood obesity such as body mass index (BMI) to predict future obesity in adolescence and adulthood. Large cohort studies, which measured obesity both in childhood and in later adolescence or adulthood, using any recognized measure of obesity were sought. Study quality was assessed. Studies were pooled using diagnostic meta-analysis methods. Fifteen prospective cohort studies were included in the meta-analysis. BMI was the only measure of obesity reported in any study, with 200,777 participants followed up. Obese children and adolescents were around five times more likely to be obese in adulthood than those who were not obese. Around 55% of obese children go on to be obese in adolescence, around 80% of obese adolescents will still be obese in adulthood and around 70% will be obese over age 30. Therefore, action to reduce and prevent obesity in these adolescents is needed. However, 70% of obese adults were not obese in childhood or adolescence, so targeting obesity reduction solely at obese or overweight children needs to be considered carefully as this may not substantially reduce the overall burden of adult obesity.

Sensorimotor dysfunction after limb fracture - An exploratory study.

BACKGROUND: Chronic pain is often associated with sensorimotor dysfunction but little is known about the early impact of limb fracture on sensory and motor performance. This exploratory study sought to assess these changes in patients with recent wrist and ankle fractures. A secondary aim was to determine the incidence of Complex Regional Pain Syndrome (CRPS) and its clinical features. METHODS: Fifty-three patients at a UK fracture centre underwent Quantitative Sensory Testing (QST), Motor Imagery (MI) and Body Perception Disturbance (BPD) assessments ≤5 weeks post-fracture (Time 1). Subjective evaluation of recovery and clinical examination for CRPS was conducted 5 weeks later (Time 2, 50 patients). Patient-reported outcomes of pain, psychological distress and limb function were collected at Times 1 and 2, and 6 months after T1 (Time 3, 36 patients, postal questionnaire). RESULTS: Quantitative sensory testing at Time 1 demonstrated cold and pressure-pain hyperalgesia in the fractured limb compared to the non-fractured side (p < 0.05). Imagined movements were reported as significantly more difficult to perform on the fractured side (p < 0.001). There was evidence of BPD in the fractured limb, similar to that found in CRPS. The incidence of CRPS was 9.4%; however, individual signs and symptoms of the condition were commonly present (70% reported ≥ one symptom). Only 33% of patients reported to being 'back to normal' 6 months after fracture with 34% reporting ongoing pain. CONCLUSIONS: Limb fracture is associated with changes in pain perceptions, motor planning, and disruption to body perception. Signs and symptoms of CRPS, ongoing pain and delayed recovery post-fracture are common. WHAT DOES THIS STUDY ADD?: In the immediate post-fracture period: Body perception disturbance is reported in the fractured limb. Imagined movements of the fractured limb are less vivid and associated with pain This study contributes to the incidence literature on CRPS.

Sertraline and desmethylsertraline in human breast milk and nursing infants.

OBJECTIVE: The purpose of this study was to determine the concentrations of sertraline and desmethylsertraline in both human breast milk and infant serum. METHOD: Breast milk samples from 12 women were collected at specific time intervals after oral doses of sertraline (25-200 mg once daily). For 11 mother-infant pairs, maternal serum levels 24 hours after a dose and their infants' serum levels 2-4 hours after nursing were ascertained by high-performance liquid chromatography. RESULTS: Sertraline and desmethylsertraline were present in all breast milk samples, with a gradient from "fore" milk to "hind" milk. The highest concentrations of sertraline were observed in hind milk 7-10 hours after maternal dose. Increasing the maternal dose of sertraline resulted in increased breast milk concentrations of both sertraline and desmethylsertraline. Detectable concentrations of sertraline were found in three nursing infants and desmethylsertraline in six. No adverse effects of exposure were observed in any infant. CONCLUSIONS: Sertraline and desmethylsertraline were present in the breast milk of nursing women treated with sertraline. Concentrations were affected by aliquot of milk sampled, time after maternal dose, and maternal daily dose. The infants' serum concentrations detected were below the detection limit of most commercial laboratories. The presence of desmethylsertraline in six infants' samples underscores the importance of metabolite monitoring in determining infant exposure. Estimates of daily infant exposure can be determined after analysis of sertraline and desmethylsertraline concentrations from one full breast at maternal serum steady state. Future studies of breast milk and infant serum samples should address these issues.

Early viral brain invasion in iatrogenic human immunodeficiency virus infection.

We report a 68-year-old man who received an IV inoculation of WBCs for an indium radionuclide scan containing 600 to 700 tissue culture infectious doses of human immunodeficiency virus type 1 (HIV-1) from an HIV-1-infected individual. The recipient immediately received zidovudine, then was switched to dideoxyinosine and interferon-alpha, but died of hepatorenal syndrome and hepatic encephalopathy 15 days later. HIV-1 cultures were positive from the recipient's blood on day 14 but not days 0, 1, and 8. At autopsy, cultures of parietal lobe isolated HIV-1. HIV-1 nucleic acid was present in several brain areas, but not in several other organs, by two independent laboratories using the polymerase chain reaction. The brain showed mild perivascular cuffing and a mild lymphocytic meningitis, but there was no evidence of glial nodules, giant cells, or white matter abnormalities. HIV-1 pg41 viral antigen was seen by immunoperoxidase staining in rare infiltrating cells within perivascular and subpial spaces. Thus, HIV-1 was isolated from brain 15 days after mistaken HIV-1 inoculation and 1 day after virus was first recovered from blood.

Psychotropic medications in lactation.

The use of psychotropic medications during lactation has not been investigated in a controlled and systematic fashion. The literature is laden with case reports and small case series containing numerous confounds that render the establishment of definitive treatment guidelines tenuous. The increasing number of women who plan to breast-feed and the high rate of psychiatric illness during the postpartum period underscore the need to develop such guidelines. A MEDLINE search was conducted for key words either in the titles or abstracts of publications citing the use of psychotropic medications in lactating women and describing the pharmacokinetics of medication excretion into breast milk. The publications identified span over three decades. The largest single study by one group of investigators examined 12 mother-infant pairs. The majority of studies report their results as a ratio of the breast milk concentration to the maternal serum concentration (milk/plasma [M/P]) ratio. Estimations that use the M/P ratio of the infant daily dose range from 0.1% to 6.2% of the maternal dose. Few studies attempt to account for the complex variations in the maternal, breast milk, and infant physiologic environments. The major confounds of the studies reviewed include (1) failure to document portion of breast milk assayed (foremilk versus hindmilk), (2) limited metabolite assay, (3) limited assay sensitivity (1-25 ng/mL), not of research quality, (4) concomitant maternal and/or infant medications, and (5) medication exposure during pregnancy. Despite these confounds, there are remarkably few reports of adverse effects on nursing infants exposed to psychotropic medications in breast milk. The limited data confirm that psychotropic medications are excreted into breast milk and that the infant is exposed to these medications. The ideal breast milk study that accounts for the confounds identified has not been completed. The complex matrix of breast milk and the changing infant metabolic capacity will require a more detailed analysis with assays of improved sensitivity. Despite the limited reports of adverse effects on nursing infants, the limitations of the available literature and minimal sample sizes make it premature to recommend specific medications from a given class. There is inadequate data on nursing infant exposure to multiple medications to support changing medication to a different agent in an otherwise stable patient. An individualized risk/benefit assessment with the empirical goal of minimizing infant exposure while maintaining maternal emotional health is the ideal approach.

The use of lithium and management of women with bipolar disorder during pregnancy and lactation.

The introduction of lithium salts almost a century ago and the subsequent approval of lithium carbonate for the treatment of patients with bipolar disorder represent one of the cornerstones of modern psychopharmacology. The onset of bipolar disorder in women often occurs during the childbearing years, which complicates the treatment decisions secondary to the possibility of conception while taking medication. The establishment of the lithium registry for fetal teratogenesis in the late 1960s ushered in a heightened level of concern for the use of lithium during the reproductive years; although, in the years to come, it has become apparent that alternative pharmacologic treatments for bipolar disorder may exceed the teratogenic risk of lithium monotherapy. In this paper, the available data on the use of antimanic medications during pregnancy and lactation are reviewed with an emphasis on providing a realistic risk/benefit assessment for medication selection and management of these patients. Treatment strategies are discussed for (1) women who are contemplating pregnancy (2) women who inadvertently conceive while taking medications (3) women who choose to become pregnant while taking medication, and (4) women who intend to breastfeed while taking medications.

Depression during pregnancy and the puerperium.

Epidemiologic studies demonstrate a twofold higher rate of depression in women than in men. The childbearing years are a time of increased risk for onset of depression in women. Pregnancy, miscarriage or pregnancy loss, infertility, and the postpartum period may challenge a woman's mental health. Virtually no life event rivals the neuroendocrine and psychosocial changes associated with pregnancy and childbirth. This paper provides a brief overview of depression during pregnancy and the postpartum period. Incidence, risk factors, and complications of depression during pregnancy and the puerperium are discussed to aid the clinician in early identification of at-risk patients. Treatment recommendations are also provided based on the available literature, clinical experience, and consideration of the possible special circumstances (i.e., breast-feeding) of this population of women.