Population-based study of the prevalence and management of self-reported high pain scores in patients with non-resected pancreatic adenocarcinoma.

BACKGROUND: Pain is a common debilitating symptom in pancreatic adenocarcinoma. This cohort study examined the use of, and factors associated with, pain-directed interventions for a high pain score in patients with non-curable pancreatic adenocarcinoma. METHODS: Administrative databases were linked and patients with non-resected pancreatic adenocarcinoma diagnosed between 2010 and 2016, who reported one or more Edmonton Symptom Assessment System (ESAS) score, were identified. A high pain score was defined as an ESAS score of at least 4. Outcomes were pain-directed interventions: opiates (in patients aged 65 years or more with universal drug coverage), nerve block and radiation therapy for a high pain score. Reduction in pain score of at least 1 point after pain-directed intervention was also evaluated. Modified Poisson regression was used to examine factors associated with pain-directed intervention. RESULTS: Among 2623 patients with a median age of 67 years, 1223 (46·6 per cent) were women, and 1621 (61·8 per cent) reported a high pain score at a median of 38 days after diagnosis. Of those with a high pain score, 75·6 per cent (688 of 910) received opiates, 13·5 per cent (219 of 1621) radiation and 1·2 per cent (19 of 1621) nerve block. The pain score decreased in 62·1 per cent of patients after administration of opiates, 73·4 per cent after radiation and all patients after nerve block. In multivariable analysis, no patient factor (age, sex, co-morbidity burden, rurality, income quintile) was associated with receipt of non-opiate pain-directed intervention for a high pain score. In patients aged at least 65 years, advanced age was associated with lower odds of opiate use. CONCLUSION: Opiates are the most common pain-directed intervention for non-curable pancreatic adenocarcinoma, whereas radiation therapy and nerve blocks are seldom used. The lack of association between pain-directed interventions and patient factors points toward practice-driven patterns.

ANTECEDENTES: El dolor es un síntoma debilitante frecuente en el adenocarcinoma de páncreas. Este estudio de cohortes examinó el uso de las intervenciones dirigidas para el tratamiento del dolor y los factores asociados a las mismas en pacientes con adenocarcinoma pancreático incurable que presentaban puntuaciones altas de dolor. MÉTODOS: Se revisaron las bases de datos administrativas y se identificaron los pacientes con adenocarcinoma pancreático no resecado diagnosticados entre 2010-2016 con puntuaciones > 1 del Sistema de Evaluación de Síntomas de Edmonton (Edmonton Symptom Assessment System, ESAS). La puntuación alta de dolor se definió como ESAS > 4. Los resultados evaluados fueron las intervenciones dirigidas contra el dolor: opiáceos (en pacientes mayores de 65 años con cobertura universal de medicamentos), bloqueo nervioso y radioterapia en el caso de puntuación alta del dolor. También se evaluó la reducción en la puntuación del dolor (> 1 punto) después de la intervención dirigida contra el dolor. Los factores asociados a la intervención contra el dolor se analizaron mediante una regresión de Poisson modificada. RESULTADOS: De los 2.623 pacientes con una mediana de edad de 67 años, 1.223 (46,6%) eran mujeres, y 1.621 (61.8%) presentaron una puntuación alta de dolor con una mediana de 38 días desde el momento del diagnóstico. De aquellos con puntuación alta de dolor, el 75,6% recibió opiáceos (n = 688/910), el 13,5% radiación (n = 219/1.621) y el 1,2% bloqueo nervioso (n = 19/1.621). La puntuación del dolor disminuyó en el 62,2% después del tratamiento con los opiáceos, en el 73,8% después de la radiación y en el 100% después del bloqueo nervioso. En el análisis multivariable, ningún factor relacionado con el paciente (edad, sexo, comorbilidades, vivir en una zona rural, quintil de ingresos) se asoció con una intervención dirigida contra dolor sin opiáceos en los casos de puntuación alta del dolor. En pacientes mayores de 65 años, la edad avanzada se asoció con menor probabilidad de uso de opiáceos. CONCLUSIÓN: Mientras que los opiáceos son la intervención dirigida contra dolor más común para el adenocarcinoma pancreático no resecable, la radioterapia y el bloqueo nervioso rara vez se usan. La falta de asociación de las intervenciones dirigidas contra el dolor con los factores del paciente apunta hacia el uso de patrones terapéuticos basados ​​en la práctica clínica.

Fluid transport and tubular intercellular spaces in reptilian kidneys.

Renal tubules of crocodiles, lizards, snakes, and turtles have intercellular spaces similar in type to those observed in the mammalian gall bladder, but different from those of mammalian renal tubules. The fluid movements across renal tubules of reptiles are correlated with the width of the tubular intercellular spaces. In the proximal tubules, where transport is always isosmotic, the spaces are open whenever the tubular epithelium is tranporting, but closed when no transport is taking place. In distal tubules, intercellular spaces are wide open when the osmolality of the urine is close to that of the blood, that is, when the fluid resorbed is almost isosmotic to the tubular fluid. The apical two-thirds of the intercellular spaces are closed when the urine is hypoosmotic. They are also closed when the tubules are not transporting, as in collapsed tubules or tubules poisoned with ouabain. Thus, as in the gall bladder, the open intercellular spaces appear to be found whenever there is fluid transport across the epithelium.

Virus-like particles in normal and tumorous tissues of Drosophila.

A new virus-like particle has been found in Drosophila. Thus far it has been detected only in electron micrographs of certain cells capable of division, such as those in larval imaginal disks, cell lines derived from imaginal disks, cells from a genetically controlled brain tumor, and adult gut cells. It appears to be slightly elliptical in shape, about 37 millimicrons by 45 millimicrons, and occurs in both the nucleus and cytoplasm. From the evidence it is suggested that the particle is a new virus.

Factors associated with receipt of symptom screening in the year after cancer diagnosis in a universal health care system: a retrospective cohort study.

Purpose: Patient-reported symptom data are collected prospectively by a provincial cancer agency to mitigate the significant symptom burden that patients with cancer experience. However, an assessment of whether such symptom screening occurs uniformly for those patients has yet to be performed. In the present study, we investigated patient, disease, and health system factors associated with receipt of symptom screening in the year after a cancer diagnosis. Methods: Patients diagnosed with cancer between 2007 and 2014 were identified. We measured whether 1 or more symptom screenings were recorded in the year after diagnosis. A multivariable modified Poisson regression with robust error variance was used to identify predictors [age, comorbidity, rurality, socioeconomic status, immigration status, cancer site, registration at a regional cancer centre (cc), and year of diagnosis] of being screened for symptoms. Results: Of 425,905 patients diagnosed with cancer, 163,610 (38%) had 1 or more symptom screening records in the year after diagnosis, and 75% survived at least 1 year. We identified variability in symptom screening by primary cancer site, regional cc, age, sex, comorbidity, material deprivation, rurality of residence, and immigration status. Patients who had been diagnosed with melanoma or endocrine cancers, who were not registered at a regional cc, who lived in the most urban areas, who were elderly, and who were immigrants were least likely to undergo symptom screening after diagnosis. Conclusions: Our evaluation of the implementation of a population-based symptom screening program in a universal health care system identified populations who are at risk for not receiving screening and who are therefore future targets for improvements in population symptom screening and better management of cancer-related symptoms at diagnosis.

A vaccine to prevent herpes zoster and postherpetic neuralgia in older adults.

BACKGROUND: The incidence and severity of herpes zoster and postherpetic neuralgia increase with age in association with a progressive decline in cell-mediated immunity to varicella-zoster virus (VZV). We tested the hypothesis that vaccination against VZV would decrease the incidence, severity, or both of herpes zoster and postherpetic neuralgia among older adults. METHODS: We enrolled 38,546 adults 60 years of age or older in a randomized, double-blind, placebo-controlled trial of an investigational live attenuated Oka/Merck VZV vaccine ("zoster vaccine"). Herpes zoster was diagnosed according to clinical and laboratory criteria. The pain and discomfort associated with herpes zoster were measured repeatedly for six months. The primary end point was the burden of illness due to herpes zoster, a measure affected by the incidence, severity, and duration of the associated pain and discomfort. The secondary end point was the incidence of postherpetic neuralgia. RESULTS: More than 95 percent of the subjects continued in the study to its completion, with a median of 3.12 years of surveillance for herpes zoster. A total of 957 confirmed cases of herpes zoster (315 among vaccine recipients and 642 among placebo recipients) and 107 cases of postherpetic neuralgia (27 among vaccine recipients and 80 among placebo recipients) were included in the efficacy analysis. The use of the zoster vaccine reduced the burden of illness due to herpes zoster by 61.1 percent (P<0.001), reduced the incidence of postherpetic neuralgia by 66.5 percent (P<0.001), and reduced the incidence of herpes zoster by 51.3 percent (P<0.001). Reactions at the injection site were more frequent among vaccine recipients but were generally mild. CONCLUSIONS: The zoster vaccine markedly reduced morbidity from herpes zoster and postherpetic neuralgia among older adults.

Persistent changes in arterial blood gases in fetal sheep.

Two anaesthetic protocols were compared using pregnant sheep. In both groups of animals, anaesthesia was induced using an intravenous (i.v.) injection of diazepam and ketamine. The ewes were then intubated for positive pressure ventilation using 0.8 L/min of nitrous oxide and 2 L/min oxygen with 1.1-1.8% halothane. If the ewe showed any signs of awakening, one of two protocols was followed. First, the halothane concentration was increased to 2-3% until the ewe was completely anaesthetized. Second, the halothane concentration was not altered, but the ewe was given doses of i.v. diazepam (0.1 mg/kg) and ketamine (1 mg/kg) until again completely anaesthetized. At the completion of surgery, maternal recovery was rapid and similar between the two groups. However, five days after surgery, the fetal arterial Po(2) and oxygen content of the fetuses receiving additional halothane (1.9 +/- 0.2 kPa and 4.4 +/- 1.0 mL/100 mL) were statistically significantly depressed when compared with the fetuses receiving additional diazepam and ketamine (2.9 +/- 0.1 kPa and 7.0 +/- 0.5 mL/100 mL). These results led us to conclude that certain anaesthetic protocols, in spite of good maternal recovery, can lead to deleterious effects upon the fetus that persist for at least five days after surgery.

Antibodies to human caudate nucleus neurons in Huntington's chorea.

Antibodies reacting with neuronal cytoplasmic antigens present in normal human caudate and subthalamic nuclei were detected in 37 of 80 probands afflicted with Huntington's disease (HD). IgG antibodies were detected by immunofluorescence using frozen sections of unfixed normal human and rat brain. Specificity of IgG binding was confirmed using pepsin F(ab')2 fragments of IgG isolated from positive sera. In vitro complement fixation of IgG antibody was detected in 22 of 31 sera tested. Neuronal cytoplasmic antigens reacting with positive HD sera were diminished after trypsin or RNAase treatment of tissue sections but were not removed by DNAase, neuraminidase, EDTA, or dithiothreitol treatment. Antibody staining of neurons could be removed after absorption with isolated caudate nucleus neurons or by using perchloroacetic acid extracts of caudate nucleus. Prevalence of antibody reacting with neuronal cytoplasm was 3% in 60 normal controls and 6% among a wide variety of patients with diverse neurological disorders. However, one-third of 33 patients with Parkinson's disease showed presence of antineuronal antibody. Among patients with HD, a significant association was noted between duration of clinical disease greater than 7 yr and titers of antibody of 1:2 or greater (P less than 0.001). When 115 family members of HD probands were tested, 30% of unaffected spouses showed presence of antineuronal antibody. 23.2% of first-degree relatives at risk for developing HD was also positive (P less than 0.001). 10.5% of second-degree relatives showed presence of antineuronal antibody. These data may support an environmental or infectious factor somehow involved in the ultimate expression of HD.

Fetal infusions of plasma cause an increase in umbilical vascular resistance in sheep.

Earlier studies suggested that the fetal placental circulation is relatively inert with fetal placental flow increasing or decreasing with perfusion pressure. Subsequent studies have demonstrated that the placenta may not be an unreactive vascular bed. The present study was undertaken to determine if plasma infusion-induced hypertension increased fetal placental flow in proportion to the driving pressure across the fetal placental circulation. Six fetal sheep were operated on at 118-122 days to place intravascular catheters and a flow sensor on the common umbilical artery. Starting 6 days later, the fetuses were infused with adult sheep plasma. During the 7-day-long infusion period, they received a total of 1515+/-217 (SD) ml of fluid and 93.2+/-12.0 g of protein. Fetal plasma protein concentrations increased from 34.2+/-2.3 to 77.0+/-9.7 g/l (P<0.0001). Fetal arterial blood pressures rose from 42+/-3 to 59+/-4 mmHg (P<0.01) and venous pressures rose from 2.2+/-0.5 to 4.8+/-0.8 mmHg (P<0.01). In spite of the large increase in driving pressure, fetal placental blood flow remained (statistically) constant (627+/-299 ml/min and 552+/-221 ml/min) while fetal umbilical resistance increased from 0.077+/-0.038 to 0.115+/-0.053 mmHg min/ml (P<0.01). On day 7, plasma renin activity had fallen from 6.7+/-4.2 ng/(ml/h) at preinfusion control to 0.6+/-0.6 ng/(ml/h) (P<0.05) and plasma angiotensin-II concentration had fallen from 33.2+/-26.6 to 6.2+/-3.9 pg/ml, although this fall was not statistically significant (P=0.07). Fetal placental flow did not increase with increased driving pressure across the fetal placental circulation. The increase in fetal placental resistance may be a response to the increase in arterial pressure since there was no increase in flow.

Predictive model for plasma concentration-versus-time profiles of investigational anticancer drugs in patients.

We report a model that provides a strong correlation between mouse toxicity data [mouse lethal dose 10% (LD10)] and human plasma concentration-versus-time (CXT) data for 22 commonly used anticancer agents. Mouse toxicity data (LD10) from two dosing schedules, daily times one and daily times seven, were evaluated for the two mouse strains BDF/1 and Swiss. Data from BDF/1 mice were selected for analysis because they were more abundant. Strong correlations were found between LD10 and human plasma CXT data for both daily times one and daily times seven dosing schedules--ln (CXT) = -1.6504 + [0.8408 X ln (LD10)], r = .84, P less than .0001, and ln (CXT) = -0.0754 + [0.8954 X ln (LD10)], r = .90, P less than .0001, respectively. These correlations may serve as useful models to predict the maximally tolerated dose of an investigational anticancer agent prior to entry into clinical trials and to assist in the selection of clinically relevant in vitro CXTs for new-agent screening against human tumors.

The sequence of changes in liver and brain in the influenza B virus mouse model of Reye's syndrome.

The time course of morphologic changes in the influenza B mouse model of Reye's syndrome is described and compared to the clinical, virologic, and biochemical changes. Following an intravenous inoculation of a lethal dose of an egg adapted strain of influenza B/Lee/40 virus, mice first showed clinical signs of lethargy and ruffled fur at 12 hours (h) post inoculation (pi). The earliest morphologic changes in the liver occurred at 12 h pi, and consisted of a slight increase in fat and loss of glycogen in hepatocytes. Over the next 36 h, the accumulation of microvesicular fat increased, and mitochondrial abnormalities such as pleomorphism and loss of dense bodies developed. There was no increase in peroxisomes. In the brain, focal cerebral edema was detected as early at 6-12 h pi. The edema, manifested as swelling of astrocytic foot processes, increased in severity with time. Endothelial cells were not abnormal. Myelin sheath splitting rarely was observed. Since changes occurred simultaneously in the liver and in the brain, we suggest that influenza B virus caused a simultaneous primary insult to both organs.

Cytomegalovirus labyrinthitis in an infant: morphological, virological, and immunofluorescent studies.

The inner ears obtained from an infant who died of severe congenital cytomegalovirus infection were examined using virological and morphological methods. The techniques of microdissection and surface preparations, immunofluorescent microscopy, and transmission and scanning electron microscopy were employed. Cytomegalovirus was isolated from the perilymph. Injury to the cochlea was minor and was confined to the first half of the basal turn. There were signs of a severe labyrinthitis of the vestibular endolymphatic system. Vestibular organs, especially the saccule and utricle, showed severe damage, with collapse of the saccular membranous wall. Inclusion-bearing cells containing cytomegalovirus antigen, as shown by immunofluorescent staining, and cytomegalovirus virions, as observed by electron microscopy, were found on the endolymphatic surface of the membranous walls, mainly in the saccule and utricle. In the utricle, the infected cells appeared to be concentrated in the regions where the so-called dark cells were located. These dark cells are similar to the proximal tubule cells in the kidney, another common target for cytomegalovirus infection.

Normal laboratory values of CSF during pregnancy.

Cerebrospinal fluid samples from 44 pregnant women undergoing spinal anesthesia for delivery were studied to determine whether an abdomen distended with a full-term fetus could alter the dynamics of lumbar CSF. The mean CSF values for opening pressure, CSF cell count, and protein concentration were all normal.

Botulism and memory.

Although botulinum toxin is thought not to affect the human CNS, previous studies have not examined those behaviors, such as memory, that have been shown to be dependent on central acetylcholine transmission. In eight patients with type A botulism, subjective analysis, bedside memory testing, and formal memory testing with Hebb's verbal sequencing test, Corsi's nonverbal sequencing test, and Buschke's verbal serial list learning test failed to demonstrate impairment in immediate and recent memory. Botulism severe enough to block peripheral nicotinic and muscarinic cholinergic transmission does not block those central cholinergic synapses involved in memory.

Atypical ocular bobbing in acute organophosphate poisoning.

Atypical ocular bobbing resulted from an intentional poisoning from dimpylate (Diazinon), an organophosphate compound. In discussing the possible foci and mechanism for atypical ocular bobbing associated with acute organophosphate poisoning, we suggest acetylcholine as a neurotransmitter substance within the ocular motor pathway. A literature review has not shown any previous reported cases with this sign.

Transverse myelitis. Retrospective analysis of 33 cases, with differentiation of cases associated with multiple sclerosis and parainfectious events.

OBJECTIVE: A study was undertaken to determine whether cases of parainfectious-associated transverse myelitis (TM) and multiple sclerosis-associated TM could be distinguished on the basis of clinical criteria, radiologic features, or cerebrospinal fluid examination. A secondary objective was to determine the incidence of TM in a US population. DESIGN: A retrospective analysis of 33 cases was conducted. Cases were classified as being related to parainfectious multiple sclerosis, or spinal cord ischemia, or idiopathic. SETTING: All cases occurring in the Albuquerque, NM, area from 1960 through 1990 were reviewed. The population base was 500,000. OUTCOME MEASURES: Clinical presentation, radiologic features, cerebrospinal fluid, recovery of ambulation and bladder function, and recurrence rates were compared. RESULTS: Thirty-three patients satisfied study criteria, corresponding to an incidence of 4.6 per million per year. Forty-five percent of these cases were categorized as parainfectious, 21% as associated with multiple sclerosis, 12% as associated with spinal cord ischemia, and 21% as idiopathic. Patients with parainfectious TM suffered from spinal shock more frequently than did those with multiple sclerosis-associated TM. Patients with parainfectious TM showed evidence of spinal cord swelling, whereas patients with multiple sclerosis-associated TM had spinal cord plaques on magnetic resonance images but none showed swelling. Oligoclonal bands were absent in patients with parainfectious TM and present in three of five patients with multiple sclerosis-associated TM. CONCLUSIONS: Parainfectious TM may be distinguishable from that associated with multiple sclerosis on the basis of presentation, findings on imaging, and the presence of cerebrospinal fluid oligoclonal bands.

Inhibition of fatty acid beta oxidation by influenza B virus and salicylic acid in mice: implications for Reye's syndrome.

Injection of concentrated influenza B/Lee/40 virus into 4-week-old Balb C mice resulted in 60% inhibition of 14C-palmitate oxidation in isolated hepatic mitochondria. Oral feeding of carnitine to infected mice prevented the inhibition of fatty acid oxidation. High concentrations of salicylic acid given orally also inhibited 14C-palmitate oxidation. Serum free fatty acid concentrations of infected mice and of those fed salicylic acid were significantly higher than in control mice. A combination of low-dose virus and low-dose salicylic acid inhibited palmitate oxidation, suggesting an additive effect on the metabolic derangement when the two agents were present simultaneously.

Familial cerebral cavernous angiomas: clinical and radiologic studies.

Cavernous angiomas are well-circumscribed cerebrovascular malformations whose natural history is poorly understood. We reviewed 5,000 cranial MRI reports of studies performed between 1986 and 1993 and retrospectively evaluated the histories and imaging studies of 29 patients whose lesions were suggestive of cavernous angiomas. Patients ranged from 3 to 66 years and 27 were of Hispanic origin. The number of malformations per patient ranged from one to 30, and 24 patients had more than one lesion. In our series, the number of lesions per patient increased at a rate of one lesion per decade of age, but the mean size of the lesions was smaller with advancing decade (p < 0.05). All patients had MRI evidence of old or recent hemorrhage confined only to the malformation and adjacent brain. In only one patient was it deemed necessary to remove the malformation. Two excluded patients with typical lesions on MRI had small arteriovenous malformations found at surgery. Thus, MRI or CT cannot identify cavernous angiomas with certainty. This study supports studies that propose that cavernous angioma-like lesions, as identified by MRI or CT, are more common in Hispanics. It is possible that patients may not be born with MRI-identifiable malformations, but with advancing age the malformations become MRI-visible through malformation growth, hemorrhage, or both. The declining size by decade favors hemorrhage rather than growth. Cavernous angiomas may be more benign than previously thought.

Tuberculous meningitis in the southwest United States: a community-based study.

This community-based study analyzed 54 patients with definite or probable tuberculous meningitis (TBM) in New Mexico from 1970 through 1990. Patients ranged in age from 4 months to 86 years. The highest age-specific incidence occurred in the elderly, but 22% of patients were less than 10 years old. Native American patients were overrepresented. Patients were as likely to live in small towns as in large urban cities. Symptoms were present for a median of 13 days before admission. The majority of patients had fevers, headache, stiff neck, and mental changes, such as confusion or lethargy. No patient was admitted comatose. Focal neurologic signs were present in 33%. Laboratory testing found hyponatremia in 79%, pulmonary infiltrates on chest x-ray in 40%, ventricular dilatation on CT or MRI in 52%, and tuberculomas in 16%. PPD skin tests were positive in 64%. CSF cultures grew Mycobacterium tuberculosis in 50%, but colony counts were always lower than 10(2)/ml. As a consequence, acid-fast stains of CSF sediment were reported as positive in only 4%. Six patients were not diagnosed during the hospitalization and died of complications. Twenty-three percent of patients who were appropriately treated also died of complications during the initial hospitalization. Tuberculous meningitis continues to be an important disease in small communities, and affects all ages and ethnic and socioeconomic backgrounds.

Increased incidence and prevalence of multiple sclerosis in Los Alamos County, New Mexico.

The incidence and prevalence of multiple sclerosis (MS) in Los Alamos County, New Mexico, were investigated because the number of reported cases appeared to have increased. The point prevalence on November 1, 1979, was 75.7 per 100,000, and average annual incidence rates for the period 1960-1969 and 1970-1979 were 3.4 and 3.7 per 100,000, respectively. The rates of MS in Los Alamos County were greater than expected from previous epidemiologic surveys of North America. The unusual ethnic composition and high socioeconomic level of the population probably contributed to the increases.

Respiratory epithelial cells masquerading as agents of primary amebic meningoencephalitis: distinguishing features.

CSF does not normally contain motile cells within flagella or cilia. When motile cells are seen in the CSF, they may be incorrectly assumed to be amebae. We studied a patient with a traumatic mucocele, in whom motile ciliated respiratory epithelial cells were seen in the CSF and within a frontal lobe brain abscess.