Workplace cardiovascular risk reduction by healthcare professionals-a systematic review.

BACKGROUND: Cardiovascular disease has a significant impact on public health and is largely preventable by addressing modifiable risk factors. As most adults spend on average half of their waking hours at work, this provides a significant opportunity to address modifiable risk factors through health promotion interventions. Healthcare professionals have the knowledge and skills to provide workplace interventions aimed at cardiovascular risk reduction. AIMS: This study was aimed to assess the literature regarding the effect of workplace interventions led by healthcare professionals on cardiovascular risk factors. METHODS: Cumulative Index to Nursing and Allied Health Literature (CINAHL), Embase, MEDLINE, PsycINFO and SPORTDiscus were systematically searched from inception to March 2021. Included studies evaluated impact of workplace interventions by healthcare professionals on cardiovascular health. Data on study design, baseline characteristics, interventions, outcomes and conclusions were extracted and qualitatively analysed. RESULTS: Forty-five studies representing 77 633 participants were included in the analysis. Healthcare professionals involved included: nurses, nurse practitioners, physicians, dietitians, pharmacists, physician assistants, medical technicians/emergency medical technicians and physiotherapists. Workplace interventions by healthcare professionals generally improved surrogate markers of cardiovascular health. Success varied based on provider and nature of the intervention. Addressing motivation and including follow-up were key factors for successful intervention to reduce cardiovascular risk factors. CONCLUSIONS: Workplace health promotion initiatives delivered by healthcare professionals may improve cardiovascular risk markers if they are evidence based and customized for target populations. More research is needed to determine clinical relevance of interventions and ideal interventions for specific employee groups.

Management of osteoradionecrosis of the jaws with pentoxifylline-tocopherol: a systematic review of the literature and meta-analysis.

Osteoradionecrosis (ORN) of the jaws remains among the most commonly encountered and challenging complications of radiotherapy to the head and neck. The purpose of this study was to provide a review of the medical management for ORN and evaluate the reported outcomes with the use of pentoxifylline and tocopherol (PENTO), by means of a systematic review and meta-analysis. The predictor variable was the use of PENTO in the treatment of ORN. The outcome variable was the proportion of full recovery or significant improvement not requiring further intervention. The likelihood function was used to combine the studies and estimate the proportion and standard deviation of each outcome by the maximum likelihood estimation. Seven studies met the inclusion criteria. A total 211 patients were treated. One hundred twenty-six patients recovered fully or improved significantly not requiring further intervention. Sixty patients remained the same, 10 were lost to follow-up, and the disease progressed in 15. The current literature supports the use of PENTO in the treatment of ORN of the jaws. Additional well-designed prospective studies are needed in order to further validate the regimen that can then be employed in the treatment of ORN.

Modified irinotecan and infusional 5-fluorouracil (mFOLFIRI) in patients with refractory advanced pancreas cancer (APC): a single-institution experience.

Pancreatic adenocarcinoma is the fourth leading cause of cancer death. Recently, MM-398 (nanoliposomal irinotecan) was shown to be associated with significant improvement in outcome measures with acceptable toxicities when combined with 5-fluorouracil (5-FU)/leucovorin (LV) compared to 5-FU/LV alone in patients failing one line of gemcitabine-based therapy. There is a paucity of data evaluating the role of irinotecan in combination with 5FU in advanced pancreas cancer (APC). We performed a retrospective analysis of all patients who received mFOLFIRI (minus bolus 5FU and LV). All patients with metastatic disease who had failed at least one line of gemcitabine-based therapy prior to receiving mFOLFIRI were included in this study. Descriptive statistics were used to assess the continuous variables and adverse events (AEs), and Kaplan-Meier methods were used to calculate the median progression-free survival (PFS) and overall survival (OS). Forty patients were included in this analysis. Patients received 1-5 lines of prior therapy (25 % with more than 3 lines of prior therapy). The mean age at diagnosis was 60, and 98 % had ECOG of 1. The mean CA 19-9 at the start of therapy was 33,169 U/ml. The median PFS was 2.59 months [95 % confidence interval (CI) (1.90, 3.54)], and OS was 4.75 months [95 % CI (3.14, 8.98)]. The most common AEs included fatigue (98 %), neuropathy (83 %), anorexia (68 %), nausea (60 %) and constipation (55 %). Grade 3 toxicities included fatigue (13 %) and rash (3 %). There were no observed grade 4 toxicities. In this single-institution retrospective analysis, mFOLFIRI was found to be both tolerable and relatively effective in a heavily pretreated patient population with APC. Future prospective studies should consider evaluating the role of mFOLFIRI in refractory APC.

Expressed Breast Milk as a Predictor of Neonatal Yeast Colonization in an Intensive Care Setting.

BACKGROUND: Yeast colonization is a predictor for invasive infection in neonates. Candida albicans and Candida parapsilosis are leading causes of invasive fungal infection (IFI) in this population. This study examines maternal breast milk as a predictor of colonization of infants with yeast. METHODS: Inclusion criteria were admission longer than 72 hours to the neonatal intensive care unit and parental consent. Cultures of expressed breast milk, when available, and swabs from oral, rectal, and inguinal sites were obtained weekly for 12 weeks, or until discharge, transfer, or death. Cultures were analyzed using standard laboratory methods. Clinical information was extracted from medical records. RESULTS: One hundred thirty infants were enrolled from February 2011 to November 2012. Cultures were obtained in 129 patients. The median (interquartile range [IQR]) gestational age was 34.4 weeks (33.1-37.1 weeks). The median (IQR) birth weight was 2157.5 g (1740-3060 g). No infants developed IFIs. Twenty-nine (22%) infants were colonized with yeast. Potential correlates for colonization in univariate analysis included exposure to antenatal steroids, postnatal antibiotics, and receipt of breast milk containing yeast. Potential correlates that remained after multivariable logistic regression included exposure to antenatal steroids and receipt of breast milk containing yeast. In cases in which yeast was recovered from an individual infant and from the breast milk received by that infant, there was only 30% concordance between yeast species. DISCUSSION: Recovery of yeast from breast milk is associated with colonization with yeast in the neonate. Because Candida transmission via breast milk had a 30% concordance, breast milk is only one of several ways colonization occurs. Further study is needed on mechanisms of colonization.

Pertuzumab for the treatment of patients with previously untreated HER2-positive metastatic breast cancer.

Pertuzumab is a humanized monoclonal antibody directed at the dimerization domain of the receptor tyrosine-protein kinase erbB-2 (HER2) receptor. It possesses a unique and complimentary mechanism of action compared to trastuzumab, which has historically been the cornerstone of therapy for HER2-amplified breast cancer. Clinical trials demonstrate improved outcomes, with minimal increases in toxicity with the addition of pertuzumab to trastuzumab in patients with HER2-positive metastatic breast cancer, indicating the advantage of dual HER2 receptor blockade. Pertuzumab is approved as first-line therapy in combination with trastuzumab and docetaxel for HER2-positive metastatic breast cancer, with future opportunities to investigate its efficacy in other stages of breast cancer, as well as in the treatment of other malignancies.

Quantification of cerebral blood flow as biomarker of drug effect: arterial spin labeling phMRI after a single dose of oral citalopram.

Arterial spin labeling (ASL) allows noninvasive quantification of cerebral blood flow (CBF), which can be used as a biomarker of drug effects in pharmacological magnetic resonance imaging (phMRI). In a double-blind, placebo-controlled crossover study, we investigated the effects of a single oral dose of citalopram (20 mg) on resting CBF in 12 healthy subjects, using ASL phMRI. Support-vector machine (SVM) analysis detected significant drug-induced reduction in CBF in brain regions including the amygdala, fusiform gyrus, insula, and orbitofrontal cortex. These regions have been shown to have abnormally elevated CBF in patients with major depression, as well as in subjects genetically prone to depression. Mixed-effects analysis on data extracted from selected regions of interest (ROIs) revealed significant drug effect only in serotonergic areas of the brain (z = -4.45, P < 0.005). These results demonstrate the utility of ASL phMRI as a biomarker of pharmacological activity of orally administered drugs in the brain.

A biobehavioural model of the night eating syndrome.

This paper will propose a biobehavioral mechanism for the Night Eating Syndrome (NES), a disorder characterized by a delayed circadian rhythm of food intake and neuroendocrine function. Food intake consists of at least 25% of daily caloric intake after the evening meal and/or at least two nighttime awakenings with ingestions per week. This will be explored by reviewing neuroimaging of brain serotonin transporters (SERT) and treatment with selective serotonin reuptake inhibitors (SSRIs). SERT binding is elevated in the midbrain of night eaters, causing dysregulation of the circadian rhythm of both food intake and neuroendocrine function. The administration of SSRIs blocks the reuptake of serotonin and restores the circadian rhythm of both food intake and neuroendocrine function. This hypothesis implies that reduction of SERT activity should increase postsynaptic serotonin transmission and relieve NES. This is precisely the effect of SSRIs. NES is a function of elevated SERT, and blocking of SERT with an SSRI resolves NES. This model of NES attests to the validity of the diagnosis of NES and the criteria by which it is identified, and it provides an explanation of the mechanism.

Health indicators among low income women who report a history of sex work: the population based Northern California Young Women's Survey.

OBJECTIVES: We examined differences in demographic characteristics, HIV related risk behaviour, prevalence of sexually transmitted infections (STI), and HIV and other health concerns among women with and without a history of sex work. METHODS: A secondary analysis of a population based, cross sectional survey of young, low income women in northern California. RESULTS: Of the 2543 women interviewed, 8.9% reported a history of sex work. These women reported more lifetime male sexual partners, were more likely to use drugs before sex, and were more likely to have a history of having sex with partners at high risk for HIV (that is, men who have sex with men, inject drugs, or were known to be HIV positive). They were significantly more likely to have positive serology for syphilis, herpes simplex virus type 2 (HSV-2), and hepatitis C regardless of their personal injecting drug use history; however, they were no more likely to have HIV, chlamydia, gonorrhoea, hepatitis A or hepatitis B infection compared to women without a history of sex work. Women with a history of sex work were significantly more likely to have a history of sexual coercion and tobacco use. CONCLUSIONS: These data measure the population prevalence of sex work among low income women and associated STI. Women with a history of sex work have health concerns beyond STI and HIV treatment and prevention.

Field Evaluation of a New Sequential Sampling Technique for Determining Apple Scab "Risk".

Most fungicide sprays applied to apple orchards in the New England states are targeted at the management of apple scab. Researchers have developed action thresholds that aid in decision-making on whether early spring fungicide applications could be eliminated without a significant increase in the incidence of fruit scab at harvest. To facilitate grower adoption of these thresholds, a simplified, sequential sampling technique in autumn to determine the "scab risk" of an orchard for the following spring was proposed in the scientific literature. However, this technique had not been evaluated in the field. In autumn 1999, 2000, and 2001, orchards were evaluated using the new sequential sampling technique to determine scab risk. Risk ratings were compared with those obtained by the original, nonsequential procedure in each orchard. Data also were examined using a simulation sequential sampling computer program to determine whether or not risk ratings would change if different trees or shoots were used. In two of the assessed orchards, "delayed-spray" experiments involving two treatments (a delayed-spray and full-spray treatment) were conducted in 2000 and 2001. Delayed-spray replicates were to receive no fungicide sprays until after the third primary infection period (but before the fourth) or until the pink stage of bud development, whichever came first; full-spray replicates received fungicide sprays starting at the green-tip stage of bud development. The sequential sampling technique provided scab-risk ratings consistent with the original, nonsequential procedure, at potentially significant time savings. Also, following the delayed-spray strategy in low-risk orchards did not result in significant differences in fruit scab at harvest compared with initiating spraying at the green-tip phenological bud stage.

Antineutrophil cytoplasmic antibody-associated necrotizing crescentic glomerulonephritis in a patient receiving treatment with etanercept for severe rheumatoid arthritis.

Etanercept is a tumor necrosis factor inhibitor used in the treatment of rheumatoid arthritis and, increasingly, in a range of other diseases. We report a case of necrotizing crescentic glomerulonephritis, associated with a positive antineutrophil cytoplasmic antibody, causing acute renal failure in a woman receiving treatment with etanercept for severe rheumatoid arthritis. Our patient was treated with steroids and cyclophosphamide following withdrawal of etanercept, with a good clinical response. Although reports of vasculitis in patients receiving treatment with etanercept are rare, this drug has been shown to up-regulate some aspects of immune function, and the possibility that this agent may precipitate or exacerbate vasculitis in some individuals has to be considered.

Ziprasidone-associated mania: a case series and review of the mechanism.

Atypical antipsychotics are now commonly used in the treatment of bipolar disorder, as they have been shown to have effects on mania as well as psychosis. Shortly after the introduction of atypical antipsychotics, several cases of associated hypomania and mania were reported. Ziprasidone is an atypical antipsychotic recently approved by the Food and Drug Administration for the treatment of psychosis. Although ziprasidone has also been shown to be effective in treating mania, it may be associated with the induction of mania or hypomania. We report four cases of mania associated with initiation of ziprasidone, which, to our knowledge, are the first reported for this drug in bipolar patients. As ziprasidone has substantial serotonergic and noradrenergic action, we hypothesize, it may more likely induce mania than other atypical antipsychotics. We advocate future studies to evaluate ziprasidone's efficacy in treating bipolar disorder and caution clinicians that induction of mania or hypomania may be possible with this agent.

Reduced edge instability and improved confinement in the MST reversed-field pinch.

Improved confinement has been achieved in the MST through control of the poloidal electric field, but it is now known that the improvement has been limited by bursts of an edge-resonant instability. Through refined poloidal electric field control, plus control of the toroidal electric field, we have suppressed these bursts. This has led to a total beta of 15% and a reversed-field-pinch-record estimated energy confinement time of 10 ms, a tenfold increase over the standard value which for the first time substantially exceeds the confinement scaling that has characterized most reversed-field-pinch plasmas.

Restoration of nucleotide excision repair in a helicase-deficient XPD mutant from intragenic suppression by a trichothiodystrophy mutation.

The UV-sensitive V-H1 cell line has a T46I substitution mutation in the Walker A box in both alleles of XPD and lacks DNA helicase activity. We characterized three partial revertants that curiously display intermediate UV cytotoxicity (2- to 2.5-fold) but normal levels of UV-induced hprt mutations. In revertant RH1-26, the efficient removal of pyrimidine (6-4) pyrimidone photoproducts from both strands of hprt suggests that global-genomic nucleotide excision repair is normal, but the pattern of cyclobutane pyrimidine dimer removal suggests that transcription-coupled repair (TCR) is impaired. To explain the intermediate UV survival and lack of RNA synthesis recovery in RH1-26 after 10 J of UV/m(2), we propose a defect in repair-transcription coupling, i.e., the inability of the cells to resume or reinitiate transcription after the first TCR event within a transcript. All three revertants carry an R658H suppressor mutation, in one allele of revertants RH1-26 and RH1-53 and in both alleles of revertant RH1-3. Remarkably, the R658H mutation produces the clinical phenotype of trichothiodystrophy (TTD) in several patients who display intermediate UV sensitivity. The XPD(R658H) TTD protein, like XPD(T46I/R658H), is codominant when overexpressed in V-H1 cells and partially complements their UV sensitivity. Thus, the suppressing R658H substitution must restore helicase activity to the inactive XPD(T46I) protein. Based on current knowledge of helicase structure, the intragenic reversion mutation may partially compensate for the T46I mutation by perturbing the XPD structure in a way that counteracts the effect of this mutation. These findings have implications for understanding the differences between xeroderma pigmentosum and TTD and illustrate the value of suppressor genetics for studying helicase structure-function relationships.

Acute mood and thyroid stimulating hormone effects of transcranial magnetic stimulation in major depression.

BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) has recently been demonstrated to have antidepressant effects. Some work suggests that rTMS over prefrontal cortex administered to healthy individuals produces acute elevations of mood and serum thyroid-stimulating hormone (TSH). We sought to determine whether single rTMS sessions would produce acute mood and serum TSH elevations in subjects with major depressions. METHODS: Under double-blind conditions et al 14 medication-free subjects with major depression received individual sessions of either active or sham rTMS. rTMS was administered over the left prefrontal cortex at 10 Hz et al 100% of motor threshold, 20 trains over 10 min. Immediately before and after rTMS sessions, subjects' mood was rated with the Profile of Mood States (POMS) and the 6-Item Hamilton Depression Scale, and blood was drawn for later analysis of TSH. Subjects and raters were blind to treatment assignment. RESULTS: The group receiving active stimulation manifested significantly greater improvement on the POMS subscale of Depression (p < or = .0055) and a trend toward greater improvement on the modified Hamilton Rating (.05 < p < or =.1). No hypomania was induced. The change in TSH from pre- to post-rTMS was significantly different between active and sham sessions. CONCLUSIONS: This blinded, placebo-controlled trial documents that individual rTMS sessions can acutely elevate mood and stimulate TSH release in patients experiencing major depressive episodes.

DNA repair excision nuclease attacks undamaged DNA. A potential source of spontaneous mutations.

Nucleotide excision repair is a general repair system that eliminates many dissimilar lesions from DNA. In an effort to understand substrate determinants of this repair system, we tested DNAs with minor backbone modifications using the ultrasensitive excision assay. We found that a phosphorothioate and a methylphosphonate were excised with low efficiency. Surprisingly, we also found that fragments of 23-28 nucleotides and of 12-13 nucleotides characteristic of human and Escherichia coli excision repair, respectively, were removed from undamaged DNA at a significant rate. Considering the relative abundance of undamaged DNA in comparison to damaged DNA in the course of the life of an organism, we conclude that, in general, excision from and resynthesis of undamaged DNA may exceed the excision and resynthesis caused by DNA damage. As resynthesis is invariably associated with mutations, we propose that gratuitous repair may be an important source of spontaneous mutations.

Histamine poisoning associated with eating tuna burgers.

CONTEXT: Histamine poisoning occurs when persons ingest fish in which bacteria have converted histidine to histamine, a process that usually can be controlled by storage at low temperatures. From 1994 to 1997, North Carolina averaged 2 cases annually; however, from July 1998 to February 1999, a total of 22 cases of histamine fish poisoning were reported. OBJECTIVES: To examine the increase in histamine case reports, identify risk factors for poisoning, and develop recommendations for prevention. DESIGN AND SETTING: Case series evaluated in North Carolina from July 1998 to February 1999. SUBJECTS: Reported case-patients with 2 of the following symptoms within 2 hours of eating tuna: rash, facial flushing, vomiting, diarrhea, dyspnea, a tight feeling in the throat, headache, or a metallic or peppery taste in the mouth. RESULTS: Twenty cases occurred during 5 outbreaks, and there were 2 single occurrences. Of the 22 persons affected, 19 (86%) sought emergency medical care. All case-patients ate tuna: 18 ate tuna burgers, 2 ate salad containing tuna, and 2 ate filets. Tuna samples (available from 3 outbreaks) had histamine levels above the Food and Drug Administration regulatory level of 50 ppm (levels were between 213 and 3245 ppm). In 19 cases, the tuna used to prepare burgers or salads was frozen and thawed more than once before serving. Violations of recommended temperature controls were identified in 2 of the 5 restaurants, accounting for 14 (64%) cases. CONCLUSIONS: Tuna burgers, a relatively new menu item in restaurants, were associated with an increase in histamine poisoning cases in North Carolina. Tuna ground for burgers can be susceptible to both temperature fluctuations and bacterial contamination.

Physiological effects of electroconvulsive therapy and transcranial magnetic stimulation in major depression.

Major depressive episodes are associated with dysregulation of various physiologic systems. Antidepressant medications alter regulation of the hormonal and sleep systems. A thorough understanding of these changes may elucidate the pathophysiologic basis of the disorder [Amsterdam et al., 1989: Psychoneuroendocrinology 14:43-62], and interventions targeted directly at these systems are being increasingly recognized as possible treatments for depression [Wong et al., 2000: Proc Natl Acad Sci USA 97:325-330; Szuba et al., 1996: Proc Am Coll Neuropsychopharmacol Ann Meet]. These physiologic systems are regulated by the major neurotransmitters implicated in the etiology of mood disorders--norepinephrine, serotonin, and dopamine. Many of the hormones of import for this article also act as neurotransmitters and thus alter cerebral activity themselves [Owens and Nemeroff, 1993: Ciba Found Symp 172:296-308; Weitzner, 1998: Psychother Psychosom 67:125-132]. Parenteral infusion of hydrocortisone [DeBattista, 2000: Am J Psychiatry 157:1334-1337] and thyrotropin-releasing hormone (TRH) [Prange et al., 1972: Lancet 2:999-1002; Marangell et al., 1997: Arch Gen Psychiatry 54:214-222; Szuba, 1996: Proc Am Coll Neuropsychopharmacol Ann Meet.] produce acute antidepressant effects. Antagonists to corticotropin-releasing hormone and repeated parenteral infusion of TRH may have antidepressant activity when given during several weeks [Wong, 2000: Proc Natl Acad Sci USA 97:325-330; Arborelius et al., 1999: J Endocrinol 160:1-12; Callahan et al., 1997: Biol Psychiatry 41:264-272]. Manipulations of the sleep system through sleep deprivation can ameliorate depression [Szuba et al., 1994: Psychiatry Res 51:283-295; see Wirz-Justice et al., 1999: Biol Psychiatry 46:445-453 for review]. Sleep deprivation has been shown in more than three dozen studies published in the last three decades to produce marked, acute antidepressant effects in the majority of depressed individuals [Wirz-Justice, et al., 1999: Biol Psychiatry 46:445-453]. Thus, examination of the effects the two nonpharmacologic treatments, electroconvulsive therapy (ECT) and transcranial magnetic stimulation (TMS), produce in these physiologic systems may help elucidate their mechanisms of action, while enhancing understanding of the neurobiology of depressive illness. We will review these physiologic changes associated with depression, the effects that manipulations of these systems can have on depressive disorders, and then describe the effects the two techniques that can stimulate the human brain in vivo, ECT and TMS, exert on these systems.

Excision of tamoxifen-DNA adducts by the human nucleotide excision repair system.

The antiestrogen tamoxifen is used in the treatment of breast cancer and has recently been recommended as a chemopreventive drug for women at high risk for breast cancer. However, women treated with the drug have an increased incidence of endometrial cancer. It has been suggested that this endometrial cancer might result from mutagenic DNA adducts, which are formed by electrophilic tamoxifen species generated by metabolic activation of the drug. Because the frequency of damage-induced mutations is strongly dependent on the repairability of the lesion, we investigated the repair of the major tamoxifen-DNA adducts by the human nucleotide excision repair system. Using the reconstituted human excision repair system and synthetic DNA substrates, we found that the four types of tamoxifen-DNA adducts detected in the endometrium were repaired with moderate to poor efficiency by nucleotide excision repair. It is concluded that individual variations in repair capacity may play a role in the development of tamoxifen-induced endometrial cancer.

Phosphorylation of ganciclovir phosphonate by cellular GMP kinase determines the stereoselectivity of anti-human cytomegalovirus activity.

A racemic mixture of ganciclovir phosphonate was resolved by stereoselective phosphorylation using GMP kinase. The R-enantiomer of ganciclovir phosphonate was active against human cytomegalovirus but the S-enantiomer was less active. We show that enantiomeric selectivity of antiviral for ganciclovir phosphonate was conferred by stereoselective phosphorylations by mammalian enzymes, not by stereoselective inhibition of DNA polymerase from human cytomegalovirus.