The role of loneliness in the association between chronic physical illness and depressive symptoms among older adults: A prospective cohort study.

BACKGROUND: Chronic physical illness increases the risk of subsequent depressive symptoms, but we know little about the mechanisms underlying this association that interventions can target. We investigated whether loneliness might explain associations between chronic illness and subsequent depressive symptoms. METHODS: We used English Longitudinal Study of Ageing data, a prospective cohort of adults over 50. Our exposure was chronic illnesses (wave two) including arthritis, cancer, diabetes, cardiovascular disease, stroke, and chronic obstructive pulmonary disease. Loneliness scores were a mediator on the short University of California, Los Angeles Loneliness Scale at wave three. Depressive symptom scores (outcome) were measured using the Centre for Epidemiologic Studies Depression Scale (wave four). We examined associations of chronic physical illness with loneliness and depressive symptoms in univariable and multivariable regression models. RESULTS: Fully-adjusted models included 2436 participants with the depression outcome and 2052 participants with the loneliness outcome. Chronic physical illness was associated with 21 % (incident rate ratio = 1.21, 95%CI = 1.03-1.42) higher depression scores at follow-up. We found no evidence of an association between chronic physical illness and loneliness and therefore did not proceed to analyses of mediation. LIMITATIONS: More prevalent chronic illnesses could have driven our results, such as cardiovascular disease. CONCLUSIONS: Chronic physical illnesses increase the risk of depressive symptoms in older adults. However, we did not find any that chronic physical illnesses were associated with an increased risk of subsequent loneliness. Therefore, interventions targeting loneliness to reduce depression in older adults with chronic physical illness may be insufficient.

A clinical evaluation of placental growth factor in routine practice in high-risk women presenting with suspected pre-eclampsia and/or fetal growth restriction.

OBJECTIVE: To evaluate the use of plasma Placental Growth Factor (PlGF), recommended by the recent NICE guidance, in women with suspected pre-eclampsia (PE) and/or fetal growth restriction (FGR). STUDY DESIGN: Non-randomised prospective clinical evaluation study in high-risk antenatal clinics in a tertiary maternity unit. METHODS: PlGF testing was performed in addition to routine clinical assessment in 260 women >20 weeks' gestation with chronic disease (hypertension, renal disease ±â€¯diabetes) with a change in maternal condition or in women with suspected FGR to determine the impact on clinical management. Results were revealed and standardised care pathways followed. MAIN OUTCOME MEASURES: Outcome of pregnancies with a low PlGF (<12 pg/ml and 13-100 pg/ml), impact on clinical service and the diagnostic accuracy of alternative PlGF cut-offs. RESULTS: 206/260 (79.2%) women had an adverse outcome (PE/birthweight < 10th centile/preterm birth). In our cohort, a low PlGF (<12 pg/ml) was associated with a shorter test-birth interval and universally (100% PPV) with an adverse pregnancy outcome, although 29/61 (47.5%) of women with PlGF < 12 pg/ml continued their pregnancy >14 days. The PlGF result altered clinical management (surveillance or timing of birth) in 196/260 (75.4%) cases. Alternative PlGF thresholds did not significantly improve diagnostic performance. CONCLUSIONS: Our evaluation confirms the value of PlGF as a diagnostic tool for placental dysfunction. However, low PlGF in isolation should not trigger iatrogenic delivery. Further research linking placental pathology, maternal disease and maternal PlGF levels is urgently needed before this test can be implemented in routine clinical practice.

IFPA Gábor Than Award Lecture: Recognition of placental failure is key to saving babies' lives.

In high-income countries, placental failure is implicated in up to 65% of cases of stillbirth. Placental failure describes the situation where the placenta cannot meet the fetus' needs and may be the end-result of a variety of underlying pathological processes evident in the placental disc, membranes and umbilical cord. These include lesions with genetic, environmental, infectious, inflammatory, mechanical, metabolic, traumatic or vascular origin. Investigation of placental tissue from stillbirths and from pregnancies at an increased risk of stillbirth has demonstrated changes in macroscopic and microscopic structure which are themselves related to abnormal placental function. A better understanding and identification of placental failure may improve the management of pregnancy complications and of pregnancies after stillbirth (which have a 5-fold increased risk of stillbirth). The majority of current antenatal tests focus on the fetus and its response to the intrauterine environment; few of these investigations reduce stillbirths in low-risk pregnancies. However, some currently used investigations reflect placental development, structure and vascular function, while other investigations employed in clinical research settings such as the evaluation of placental structure and shape have a good predictive value for adverse fetal outcome. In addition, recent studies suggest that biomarkers of placental inflammation and deteriorating placental function can be detected in maternal blood suggesting that holistic evaluation of placental structure and function is possible. We anticipate that development of reliable tests of placental structure and function, coupled to assessment of fetal wellbeing offer a new opportunity to identify pregnancies at risk of stillbirth and to direct novel therapeutic strategies to prevent it.

Prescribing indicators: what can Canada learn from European countries?

BACKGROUND: Drug therapy can improve patients' quality of life and health outcomes; however, underuse, overuse and inappropriate use of drugs can occur. Systematic examination of potential opportunities for improving prescribing and medication use is needed. OBJECTIVE: To convene a diverse group of stakeholders to learn about and discuss advantages and limitations of data sources, tools and methods related to drug prescribing indicators; foster methods to assess safe, appropriate and cost-effective prescribing; increase awareness of international organizations who develop and apply performance indicators relevant to Canadian researchers, practitioners and decision-makers; and provide opportunities to apply information to the Canadian context. METHODS: Approximately 50 stakeholders (health system decision-makers, senior and junior researchers, healthcare professionals, graduate students) met June 1-2, 2009 in Halifax, Canada. Four foundational presentations on evaluating quality of prescribing were followed by discussion in pre-assigned breakout groups of a prepared case (either antibiotic use or prescribing for seniors), followed by feedback presentations. RESULTS: Many European countries have procedures to develop indicators for prescribing and quality use of medicines. Indicators applied in diverse settings across the European Union use various mechanisms to improve quality, including financial incentives for prescribers. CONCLUSION: Further Canadian approaches to develop a system of Canadian prescribing indicators would enable federal/provincial/territorial and international comparisons, identify practice variations and highlight potential areas for improvement in prescribing, drug use and health outcomes across Canada. A more standardized system would facilitate cross-national research opportunities and enable Canada to examine how European countries use prescribing indicators, both within their country and across the European Union.

Reduction of glial glutamate transporters in the parietal cortex and hippocampus of the EL mouse.

There is extensive experimental evidence indicating a crucial role for glutamate in epileptogenesis and epileptic activity. The glial glutamate transporters GLT1 and GLAST are proposed to account for the majority of extracellular glutamate re-uptake. In the present study, polyclonal antibodies specific to GLT1 and GLAST were generated and characterized, revealing distribution patterns for the two transporters confirming those previously reported. In situ hybridization and immunoblotting were then used to compare levels of these two transporters in the parietal cortex and hippocampus of unstimulated and stimulated EL mice with DDY control mice. Additionally, HPLC determined tissue glutamate concentrations in the same regions of these animals. These experiments revealed reductions in GLT1 mRNA and protein in the parietal cortex of unstimulated and stimulated EL mice compared with DDY controls, accompanied by an increase in tissue glutamate concentration in the stimulated EL mice group. GLT1 mRNA was also reduced in the CA3 hippocampal subfield of both unstimulated and stimulated EL mice. GLAST protein was reduced in the hippocampus of the stimulated EL mice group, while no changes in GLAST mRNA or protein were detected in the parietal cortex of EL mice when compared with DDY controls. The glial glutamate transporter down-regulation reported here may play a role in seizure initiation, spread and maintenance in the EL mouse.

Glial glutamate transporter mRNAs in the genetically absence epilepsy rat from Strasbourg.

Recent studies support a critical role for the glutamatergic system and glutamate transporters in the pathogenesis of epilepsy. The glial glutamate transporters GLT-1 (L-glutamate transporter) and GLAST (L-glutamate/L-aspartate transporter) are known to be responsible for the majority of glutamate reuptake from the synaptic cleft and constitute one mechanism by which extracellular glutamate levels may be controlled. The present study therefore compared GLT-1 and GLAST mRNA levels in the genetically absence epilepsy rat from Strasbourg (GAERS) with those of age-matched non-epileptic controls. The GAERS rat has been proposed as an animal model of inherited human absence epilepsy, displaying recurrent, generalised, non-convulsive seizures that originate from thalamic and cortical structures. In situ hybridisation with 35S-labelled oligonucleotide probes demonstrated substantial and significant increases in GLT-1 mRNA levels in the ventromedial nucleus of the thalamus (VM) and the subthalamic nucleus (STN) of GAERS rats. Increases in GLAST mRNA were found in the primary somatosensory cortex (SS1) and temporal cortex (Te) of GAERS. These data, along with previous studies, suggest that regional imbalances in GABAergic and glutamatergic systems may be associated with the pathogenesis of absence seizures in GAERS.

Anaplastic and sarcomatoid carcinoma of the small intestine: an unusual tumor.

Primary malignant tumors of the small intestine are rare, and sarcomatoid carcinomas have rarely been reported at this site. Anaplastic and sarcomatoid carcinomas are well described in the upper aerodigestive tract, particularly in the esophagus and the larynx. The authors report a case of anaplastic and sarcomatoid carcinoma of the ileum presenting as gastrointestinal bleeding. Their patient and the literature suggest that these tumors are much more aggressive than other small intestinal tumors. The importance of a systematic diagnostic approach in diagnosing these tumors is also discussed.

Fine-needle aspiration cytology of ameloblastic carcinoma of the maxilla: a rare tumor.

This report describes the cytologic, histologic, and clinical features of an ameloblastic carcinoma of the maxilla occurring in an 83-yr-old white male. A fine-needle aspiration revealed malignant cells with a predominantly small cell type morphology. There were also a few cells of a second type which were more polygonal to spindled with oval to elongate nuclei. A focal amorphous blue-grey matrix was noted in association with these cells. Although the biopsy showed prominent areas of squamous metaplasia, no squamous cells were seen in the cytologic sample.

Lung cancer in nonsmoking women. Histology and survival patterns.

BACKGROUND: Despite the widespread view that important clinical and etiologic differences exist between histologic categories of lung cancer, few studies have examined the accuracy of hospital-reported pathologic diagnoses of lung cancer. METHODS: A review of pathologic material and an assessment of survival patterns were conducted in conjunction with a recently completed case-control study of lung cancer among nonsmoking women in Missouri. Using established protocols, tissue slides from tumors of 482 patients were reviewed by 3 pathologists. RESULTS: Adenocarcinoma was the most common histologic type among former smokers and lifetime nonsmokers. The overall agreement rate between the original and review diagnoses was 65.6%. The positive predictive value ranged from 0.33 for bronchioalveolar carcinomas to 0.84 for adenocarcinomas. Agreement rates for small, medium, and large hospitals were 63.1, 66.6, and 66.2%, respectively. Survival rates were highest for bronchioalveolar carcinoma and lowest for small cell carcinoma. CONCLUSION: Given the importance of lung cancer to public health and the need to examine risk by histologic type, these data indicate that pathologic review of registry-reported lung cancer cases may be an important component of large scale studies of etiology.

Cervical inflammation and preterm delivery in pregnant women with a history of preterm delivery.

BACKGROUND: A previous preterm delivery is a risk factor for preterm delivery in a subsequent pregnancy. We tested the hypothesis that evidence of inflammation on a Papanicolaou smear obtained during pregnancy is a risk factor for preterm delivery for women with a history of preterm delivery. METHODS: We studied women who had two singleton deliveries at a university hospital during an 8-year period. Women eligible for our study were those whose first delivery was preterm (< 37 weeks of gestation) and for whom a Papanicolaou smear was obtained during the second pregnancy. These smears were examined for evidence of inflammation by a cytopathologist. Information about the second pregnancy was obtained by chart review. RESULTS: The cytopathologist reviewed Papanicolaou smears from 92 study pregnancies and found evidence of cervical inflammation on 34 smears (37 percent). Preterm delivery ended 24 (26.1 percent) of the second pregnancies. The incidence of preterm delivery in women with inflammation on Papanicolaou smear was 41.2 percent compared with an incidence of 17.2 percent in women without inflammation (relative risk of 2.40 with a 95 percent confidence interval of 1.19 to 4.83). This association remained significant after controlling for potential confounding variables. A stratified analysis found that the association of cervical inflammation with preterm delivery was limited to women who had systemic exposure to an antibiotic during pregnancy. CONCLUSION: Among pregnant women with a history of preterm delivery, evidence of inflammation on Papanicolaou smear was associated with an increased risk of preterm delivery. If replicated in other studies, this finding might have implications for the management of pregnancies in women with a history of preterm delivery.

Inflammation on the cervical Papanicolaou smear: the predictive value for infection in asymptomatic women.

BACKGROUND: The clinical significance of inflammation on the cervical Papanicolaou (Pap) smear of asymptomatic women is unknown. This study assessed the possible association between inflammation on Pap smears with the presence of cervical/vaginal pathogens. METHODS: A questionnaire was given to 290 asymptomatic women seen for routine gynecologic examination, including Pap smear, in a primary care setting. The women were tested for the presence of Candida species, Trichomonas vaginalis, Gardnerella vaginalis, Neisseria gonnorrhoeae, and Chlamydia trachomatis. RESULTS: Recovery of Chlamydia and Trichomonas was more frequent in women with inflammation on Pap smear than in women without inflammation, but the positive predictive value of inflammation was only 7% for Chlamydia and 14% for Trichomonas. Seventy-one percent of the women with inflammation had no evidence of any of the organisms. After a 6-month follow-up period, women with inflammation on Pap smear were no more likely than their matched counterparts without inflammation to return for a clinic visit with symptoms of vaginitis. CONCLUSIONS: In this study, inflammation on Pap smear had a relatively low predictive value for the presence of vaginal pathogens in asymptomatic women.

Echinococcosis (hydatid disease) in Missouri: diagnosis by fine-needle aspiration of a lung cyst.

Echinococcus granulosus was diagnosed by fine-needle aspiration cytology of a lung cyst in a 6-yr-old white female in central Missouri. No adverse reaction occurred following the aspiration. The cytologic sample yielded clear fluid containing numerous clearly identifiable protoscoleces diagnostic for echinococcosis using routine PAP staining. Since hydatid disease is extremely uncommon in the Midwest, it had not initially been considered in the differential diagnosis. The infection was probably not indigenous to Missouri, since the patient lived the first 3 1/2 yr of life in Alaska, where the organism is endemic. This can only be speculative, however, since echinococcal organisms are found in wildlife in the Midwest.

Pulmonary talc granulomatosis in a cocaine sniffer.

The development of pulmonary granulomatosis following intravenous injection of medications intended for oral use has been well described previously. Talc is the most commonly implicated agent. We present a case of talc granulomatosis which developed in a patient following cocaine sniffing and suggest that this may be the cause of development of granulomata in drug addicts who deny any history of intravenous drug abuse.

Meningeal metastasis of squamous-cell carcinoma of the uterine cervix: case report and review of the literature.

Cervical squamous carcinoma metastatic to the central nervous system is an uncommon occurrence. Only eight such cases are reported in the literature. This is a case report of such a metastasis with emphasis on the cytologic features seen in the tumor cells found in the spinal fluid, along with a review of the literature.

Papanicolaou smears without endocervical cells. Are they inadequate?

The retrieval of columnar endocervical cells from the squamocolumnar junction has generally been considered to be a measure of the adequacy of a Papanicolaou smear; this implies that, if endocervical cells are absent from the smear, the examination for cervical cancer is less than optimal and should be repeated. A study was undertaken to determine if women with serial Papanicolaou smears without endocervical cells showed an increased rate of development of cervical atypia in subsequent smears. The smears of 18,914 women were evaluated for the presence or absence of endocervical cells and for the subsequent development of an abnormal smear over a four-year study period. No differences were found in the rates of atypia between women with and those without endocervical cells on serial Papanicolaou smears. Women with prior Papanicolaou smears without endocervical cells were much more likely to have a subsequent Papanicolaou smear without endocervical cells. Although no difference was found in the incidence of cervical atypia in the two groups during this short study period, these results should be considered to be preliminary.

Improved yield of endocervical cells on Papanicolaou smears in a residency setting.

Techniques employed in the collection of cervical cytology show a wide range of detection rates of endocervical cells. The presence of endocervical cells is currently considered to be an important factor in assessing the adequacy of a Papanicolaou smear. In a clinical trial in a university-based family practice center, the yield of endocervical cells was compared during several interventions. These interventions included wetting the cotton swab, changing the number of slides collected, and introducing an extended tip spatula. Clinic physicians were divided into experimental and control groups. Significant improvement in the yield of endocervical cells was found in the group using the extended tip spatula. There was no consistent effect of level of residency training on endocervical cell yield during any intervention.

Adenocarcinoma of the male urethra with associated nephrogenic metaplasia. Case report and review of the literature.

Nephrogenic metaplasia is an uncommon sequela of chronic bladder irritation. The case described herein represents the second reported in the bulbomembranous urethra of the male. Important questions are raised regarding the premalignant potential of nephrogenic metaplasia. A review of the literature on adenocarcinoma of the male urethra and also of nephrogenic metaplasia of the bladder and urethra is presented.

Studies of the extracellular proteolytic activity produced by Propionibacterium acnes.

Of several commercial media tested, trypticase soya both containing 0.4% (w/v) D-sorbitol was superior as a growth medium for the production of extracellular proteinase by Propionibacterium acnes (strain P-37). Extracellular proteinase, production of which was shown to be growth-associated by both batch and continuous culture studies, was partially purified by 70% (NH4)2SO4 saturation. Sephadex G-75 chromatography and ion exchange on DEAE-Sephadex A-50. It was shown to be a heterogeneous mixture of at least three molecular species of enzyme. Proteinase I was inhibited by EDTA (10(-3) mol/l) and PMSF (5 millimol/l) and stimulated by CaCl2 (190% at 10(-3) mol/l). It had a molecular weight of 20 to 30000 and a broad pH optimum from 6.5 to 7.5. Proteinase II was an alkaline proteinase with a molecular weight of 30 to 40000 which was not significantly inhibited by EDTA (10(-2) mol/l) nor stimulated by CaCl2. Proteinase III represented a minor proportion of the recovered proteolytic activity, had a molecular weight of 20 to 30000 and was most active in the alkaline pH range. This enzyme was inhibited by EDTA (10(-4) mol/l) and PMSF (5 millimol/l), and stimulated by CaCl2 (250% at 10(-2) mol/l).

Epidemic measles in Shetland during 1977 and 1978.

During 1977 and 1978 an unusual epidemic of measles occurred in Shetland, affecting 1032 (5%) of the population. All age groups were represented, and 309 cases occurred in people over 15. Geographical distribution of notified cases ranged from 1% to over one-third of the population aged under 65. All the recognised complications occurred, with a significant excess of respiratory troubles (p less than 0 . 05). Complications were much less common in female patients (p less than 0 . 05). Only about 30% of children under 5 had been vaccinated against the disease, and, based on a sample population, vaccination was found to have had a protective effect of 92%. On cost effectiveness alone, uptake of vaccination by a community as susceptible as that of Shetland should clearly be encouraged and probably given high priority.