Elucidating the Roles of Maternal Overcontrol and Warmth in the Development of Childhood Anxiety and Depression: A Moderated Mediation Framework.

Studies have linked childhood anxiety and depression with parenting characterized by high control and low warmth. However, few studies have examined how control and warmth may work together to influence internalizing symptoms in children. Therefore, the goal of this study was to examine the moderating effect of warmth on the relationship between overcontrol and anxiety and depressive symptoms, as well as whether negative thoughts serve as a mediator of these pathways. A total of 182 fourth and fifth grade children completed measures of maternal parenting behavior, negative thoughts, and anxiety and depressive symptoms. Results showed an interaction between overcontrol and warmth for depressive but not anxiety symptoms. Furthermore, low warmth increased the strength of the mediating relationship between overcontrol and depression via thoughts of personal failure. Findings may signal a need for early interventions to address parenting behaviors, such as controlling behaviors, in parents of children at risk for internalizing difficulties.

Do Social Threat Cognitions Decrease With School-Based CBT and Predict Treatment Outcome in Adolescents With Social Anxiety Disorder?

Evidence suggests that Social Anxiety Disorder (SAD) is less responsive to cognitive behavioral treatment (CBT) compared to other anxiety disorders. Therefore, exploring what might facilitate clinical benefit is essential. Social threat cognitions, characterized by exaggerated perceptions of negative evaluation by others, may be one important avenue to examine. The current study investigated whether youths' social threat cognitions decreased with Skills for Academic and Social Success (SASS), a group, school-based CBT designed for SAD, and whether decreases predicted SAD severity and treatment response. Participants included 138 high school students with SAD randomly assigned to SASS, or a nonspecific school counseling intervention. SASS participants showed significantly decreased social threat cognitions at 5-month follow-up. Treatment responders had significantly greater reductions in social threat cognitions compared to nonresponders at post-intervention and follow-up. These findings suggest that social threat cognitions may be important to assess and monitor when treating youth with SAD.

Effects of cognitive behavioral therapy for insomnia and armodafinil on quality of life in cancer survivors: a randomized placebo-controlled trial.

PURPOSE: Cancer-related insomnia is associated with diminished quality of life (QOL), suggesting that improvement in insomnia may improve QOL in cancer survivors. Cognitive behavioral therapy for insomnia (CBT-I) has been shown to improve insomnia, but less is known regarding its effect on QOL and whether improvement in insomnia corresponds to improved QOL. The present analysis examines the effects of CBT-I, with and without armodafinil, on QOL both directly and indirectly through improvements of insomnia. METHODS: This is an analysis of 95 cancer survivors for a specified secondary aim of a four-arm randomized controlled trial assessing the combined and individual effects of CBT-I and armodafinil to improve insomnia. QOL and insomnia severity were assessed before, during the intervention, at post-intervention, and 3 months later by Functional Assessment of Cancer Therapy-General and Insomnia Severity Index, respectively. RESULTS: Mean change in QOL from pre- to post-intervention for CBT-I + placebo, CBT-I + armodafinil, armodafinil, and placebo was 9.6 (SE = 1.8; p < 0.0001), 11.6 (SE = 1.8; p < 0.0001), -0.2 (SE = 3.2; p = 0.964), and 3.3 (SE = 2.0; p = 0.124), respectively. ANCOVA controlling for pre-intervention scores showed that participants receiving CBT-I had significantly improved QOL at post-intervention compared to those not receiving CBT-I (p < 0.0001, effect size = 0.57), with benefits being maintained at the 3-month follow-up. Path analysis revealed that this improvement in QOL was due to improvement in insomnia severity (p = 0.002), and Pearson correlations showed that changes in QOL from pre- to post-intervention were significantly associated with concurrent changes in insomnia severity (r = -0.56; p < 0.0001). Armodafinil had no effect on QOL for those who did or did not receive it (p = 0.976; effect size = -0.004). CONCLUSION: In cancer survivors with insomnia, CBT-I resulted in clinically significant improvement in QOL via improvement in insomnia. This improvement in QOL remained stable even 3 months after completing CBT-I. IMPLICATIONS FOR CANCER SURVIVORS: Considering the high prevalence of insomnia and its detrimental impact on QOL in cancer survivors and the effectiveness of CBT-I in alleviating insomnia, it is important that evidence-based non-pharmacological sleep interventions such as CBT-I be provided as an integral part of cancer care.

Nausea and disturbed sleep as predictors of cancer-related fatigue in breast cancer patients: a multicenter NCORP study.

PURPOSE: Cancer-related fatigue (CRF) is a prevalent and distressing side effect of cancer and its treatment that remains inadequately understood and poorly managed. A better understanding of the factors contributing to CRF could result in more effective strategies for the prevention and treatment of CRF. The objectives of this study were to examine the prevalence, severity, and potential predictors for the early onset of CRF after chemotherapy cycle 1 in breast cancer patients. METHODS: We report on a secondary data analysis of 548 female breast cancer patients from a phase III multi-center randomized controlled trial examining antiemetic efficacy. CRF was assessed by the Brief Fatigue Inventory at pre- and post-chemotherapy cycle 1 as well as by the four-day diary. RESULTS: The prevalence of clinically relevant post-CRF was 75%. Linear regression showed that pre-treatment CRF, greater nausea, disturbed sleep, and younger age were significant risk factors for post-CRF (adjusted R2 = 0.39; P < 0.0001). Path modeling showed that nausea severity influenced post-CRF both directly and indirectly by influencing disturbed sleep. Similarly, pre-treatment CRF influenced post-CRF directly as well as indirectly through both nausea severity and disturbed sleep. Pearson correlations showed that changes in CRF over time were significantly correlated with concurrent changes in nausea severity (r = 0.41; P < 0.0001) and in disturbed sleep (r = 0.20; P < 0.0001). CONCLUSION: This study showed a high prevalence (75%) of clinically relevant CRF in breast cancer patients following their initial chemotherapy, and that nausea severity, disturbed sleep, pre-treatment CRF, and age were significant predictors of symptom.

Total-Body Irradiation Exacerbates Dissemination of Cutaneous Candida Albicans Infection.

Exposure to radiation, particularly a large or total-body dose, weakens the immune system through loss of bone marrow precursor cells, as well as diminished populations of circulating and tissue-resident immune cells. One such population is the skin-resident immune cells. Changes in the skin environment can be of particular importance as the skin is also host to a number of commensal organisms, including Candida albicans , a species of fungus that causes opportunistic infections in immunocompromised patients. In a previous study, we found that a 6 Gy sublethal dose of radiation in mice caused a reduction of cutaneous dendritic cells, indicating that the skin may have a poorer response to infection after irradiation. In this study, the same 6 Gy sublethal radiation dose led to a weakened response to a C. ablicans cutaneous infection, which resulted in systemic dissemination from the ear skin to the kidneys. However, this impaired response was mitigated through the use of interleukin-12 (IL-12) administered to the skin after irradiation. Concomitantly with this loss of local control of infection, we also observed a reduction of CD4+ and CD8+ T cells in the skin, as well as the reduced expression of IFN-γ, CXCL9 and IL-9, which influence T-cell infiltration and function in infected skin. These changes suggest a mechanism by which an impaired immune environment in the skin after a sublethal dose of radiation increases susceptibility to an opportunistic fungal infection. Thus, in the event of radiation exposure, it is important to include antifungal agents, or possibly IL-12, in the treatment regimen, particularly if wounds are involved that result in loss of the skin's physical barrier function.

Sexualized behaviors in cohorts of children in the child welfare system.

The current retrospective archival study investigated the patterns of normative sexualized behavior (NSB), problematic sexualized behavior (PSB), and sexual perpetration for three age cohorts of boys and girls in a high-risk child welfare sample. All children in the present sample had exhibited some form of PSB in the past. We hypothesized that the incidence rates (IR) of NSBs would increase linearly from the early childhood cohort (Ages 2/3-7) to the middle childhood cohort (Ages 8-11) to the preadolescence/adolescence cohort (Ages 12-17), for girls and boys. Although the base rate of sexual behaviors generally increases as children age, children tend to hide sexual behaviors starting at an early age. We therefore hypothesized that a concave quadratic trend would be evident for most PSBs. We further predicted that older children would have a greater incidence of PSB, as well as more victims, compared with younger children. We found the predicted upward linear trend for NSB for both girls and boys, with minimal IR differences between the early childhood and middle childhood cohorts. IRs were remarkably high and comparable across age groups for both boys and girls, with respect to the same three PSBs. For the two perpetration history variables, there was a concave effect, with girls and boys in the middle childhood cohort exhibiting the lowest IR. Results are explained in the context of previously established patterns of sexualized behavior, as well as the reporting of such behaviors.

Interleukin-12 preserves the cutaneous physical and immunological barrier after radiation exposure.

The United States continues to be a prime target for attack by terrorist organizations in which nuclear detonation and dispersal of radiological material are legitimate threats. Such attacks could have devastating consequences to large populations, in the form of radiation injury to various human organ systems. One of these at risk organs is the cutaneous system, which forms both a physical and immunological barrier to the surrounding environment and is particularly sensitive to ionizing radiation. Therefore, increased efforts to develop medical countermeasures for treatment of the deleterious effects of cutaneous radiation exposure are essential. Interleukin-12 (IL-12) was shown to elicit protective effects against radiation injury on radiosensitive systems such as the bone marrow and gastrointestinal tract. In this article, we examined if IL-12 could protect the cutaneous system from a combined radiation injury in the form of sublethal total body irradiation and beta-radiation burn (ß-burn) directly to the skin. Combined radiation injury resulted in a breakdown in skin integrity as measured by transepidermal water loss, size of ß-burn lesion and an exacerbated loss of surveillant cutaneous dendritic cells. Interestingly, intradermal administration of IL-12 48 h postirradiation reduced transepidermal water loss and burn size, as well as retention of cutaneous dendritic cells. Our data identify IL-12 as a potential mitigator of radiation-induced skin injury and argue for the further development of this cytokine as a radiation countermeasure.

A phase III randomized, placebo-controlled study of topical amitriptyline and ketamine for chemotherapy-induced peripheral neuropathy (CIPN): a University of Rochester CCOP study of 462 cancer survivors.

PURPOSE: Chemotherapy-induced peripheral neuropathy (CIPN) occurs in as high as 70% of patients receiving certain types of chemotherapy agents. The FDA has yet to approve a therapy for CIPN. The aim of this multicenter, phase III, randomized, double-blind, placebo-controlled trial was to investigate the efficacy of 2% ketamine plus 4% amitriptyline (KA) cream for reducing CIPN. METHODS: Cancer survivors who completed chemotherapy at least 1 month prior and had CIPN (>4 out of 10) were enrolled (N=462). CIPN was assessed using average scores from a 7-day daily diary that asks patients to rate the average "pain, numbness, or tingling in [their] hands and feet over the past 24 h" on an 11-point numeric rating scale at baseline and 6 weeks post intervention. ANCOVA was used to measure differences in 6-week CIPN with effects including baseline CIPN, KA treatment arm, and previous taxane therapy (Y/N). RESULTS: The KA treatment showed no effect on 6-week CIPN scores (adjusted mean difference=-0.17, p=0.363). CONCLUSIONS: This study suggests that KA cream does not decrease CIPN symptoms in cancer survivors.

18F-fluorodeoxyglucose positron emission tomography-computed tomography imaging in the management of Merkel cell carcinoma: a single-institution retrospective study.

BACKGROUND: Merkel cell carcinoma (MCC) is among the deadliest of cutaneous malignancies. A lack of consensus evaluation and treatment guidelines has hindered management of this disease. The utility of simultaneous positron emission tomography and computed tomography (PET/CT) has been demonstrated for a variety of tumors yet remains underinvestigated for MCC. OBJECTIVES: To report the value of fluorodeoxyglucose PET/CT imaging in the initial staging and ongoing management of individuals with MCC and to determine whether any patient or tumor characteristics may predict when PET/CT is more likely to have greater influence on medical decision-making. MATERIALS AND METHODS: A single-institution retrospective chart review was conducted of all patients diagnosed with MCC who underwent FDG-PET/CT scanning from 2007 to 2010. The outcome of each of these studies was evaluated as to the influence on patient staging and management. Patient clinical information and information on gross and microscopic tumor characteristics were collected and analyzed. RESULTS: Twenty patients underwent 39 PET/CT scans. Results of PET/CT imaging revealed previously unknown information related to MCC in four (20%) patients, leading to changes in management in three of these four cases. Three previously unknown neoplasms were detected. CONCLUSION: Fluorodeoxyglucose-positron emission tomography and computed tomography is a valuable tool for initial staging and to assess response to therapy of patients diagnosed with MCC. Larger prospective studies would be required to establish the optimal timing for this imaging modality.

Curcumin for radiation dermatitis: a randomized, double-blind, placebo-controlled clinical trial of thirty breast cancer patients.

Radiation dermatitis occurs in approximately 95% of patients receiving radiotherapy (RT) for breast cancer. We conducted a randomized, double-blind, placebo-controlled clinical trial to assess the ability of curcumin to reduce radiation dermatitis severity in 30 breast cancer patients. Eligible patients were adult females with noninflammatory breast cancer or carcinoma in situ prescribed RT without concurrent chemotherapy. Randomized patients took 2.0 grams of curcumin or placebo orally three times per day (i.e., 6.0 grams daily) throughout their course of RT. Weekly assessments included Radiation Dermatitis Severity (RDS) score, presence of moist desquamation, redness measurement, McGill Pain Questionnaire-Short Form and Symptom Inventory questionnaire. The 30 evaluable patients were primarily white (90%) and had a mean age of 58.1 years. Standard pooled variances t test showed that curcumin reduced RDS at end of treatment compared to placebo (mean RDS = 2.6 vs. 3.4; P = 0.008). Fisher's exact test revealed that fewer curcumin-treated patients had moist desquamation (28.6% vs. 87.5%; P = 0.002). No significant differences were observed between arms for demographics, compliance, radiation skin dose, redness, pain or symptoms. In conclusion, oral curcumin, 6.0 g daily during radiotherapy, reduced the severity of radiation dermatitis in breast cancer patients.

Characterization of skin reactions and pain reported by patients receiving radiation therapy for cancer at different sites.

BACKGROUND: Skin reactions and pain are commonly reported side effects of radiation therapy (RT). OBJECTIVE: To characterize RT-induced symptoms according to treatment site subgroups and identify skin symptoms that correlate with pain. METHODS: A self-report survey-adapted from the MD Anderson Symptom Inventory and the McGill Pain Questionnaire--assessed RT-induced skin problems, pain, and specific skin symptoms. Wilcoxon Sign Ranked tests compared mean severity or pre- and post-RT pain and skin problems within each RT-site subgroup. Multiple linear regression (MLR) investigated associations between skin symptoms and pain. RESULTS: Survey respondents (N = 106) were 58% female and on average 64 years old. RT sites included lung, breast, lower abdomen, head/neck/brain, and upper abdomen. Only patients receiving breast RT reported significant increases in treatment site pain and skin problems (P < or = .007). Patients receiving head/neck/brain RT reported increased skin problems (P < .0009). MLR showed that post-RT skin tenderness and tightness were most strongly associated with post-RT pain (P = .066 and P = .122, respectively). LIMITATIONS: Small sample size, exploratory analyses, and nonvalidated measure. CONCLUSIONS: Only patients receiving breast RT reported significant increases in pain and skin problems at the RT site while patients receiving head/neck/brain RT had increased skin problems but not pain. These findings suggest that the severity of skin problems is not the only factor that contributes to pain and that interventions should be tailored to specifically target pain at the RT site, possibly by targeting tenderness and tightness. These findings should be confirmed in a larger sampling of RT patients.

Exposure to ionizing radiation induces the migration of cutaneous dendritic cells by a CCR7-dependent mechanism.

In the event of a deliberate or accidental radiological emergency, the skin would likely receive substantial ionizing radiation (IR) poisoning, which could negatively impact cellular proliferation, communication, and immune regulation within the cutaneous microenvironment. Indeed, as we have previously shown, local IR exposure to the murine ear causes a reduction of two types of cutaneous dendritic cells (cDC), including interstitial dendritic cells of the dermis and Langerhans cells of the epidermis, in a dose- and time-dependent manner. These APCs are critical regulators of skin homeostasis, immunosurveillance, and the induction of T and B cell-mediated immunity, as previously demonstrated using conditional cDC knockout mice. To mimic a radiological emergency, we developed a murine model of sublethal total body irradiation (TBI). Our data would suggest that TBI results in the reduction of cDC from the murine ear that was not due to a systemic response to IR, as a loss was not observed in shielded ears. We further determined that this reduction was due, in part, to the upregulation of the chemoattractant CCL21 on lymphatic vessels as well as CCR7 expressed on cDC. Migration as a potential mechanism was confirmed using CCR7(-/-) mice in which cDC were not depleted following TBI. Finally, we demonstrated that the loss of cDC following TBI results in an impaired contact hypersensitivity response to hapten by using a modified contact hypersensitivity protocol. Taken together, these data suggest that IR exposure may result in diminished immunosurveillance in the skin, which could render the host more susceptible to pathogens.

Cancer-related stress and complementary and alternative medicine: a review.

A cancer diagnosis elicits strong psychophysiological reactions that characterize stress. Stress is experienced by all patients but is usually not discussed during patient-healthcare professional interaction; thus underdiagnosed, very few are referred to support services. The prevalence of CAM use in patients with history of cancer is growing. The purpose of the paper is to review the aspects of cancer-related stress and interventions of commonly used complementary and alternative techniques/products for amelioration of cancer-related stress. Feasibility of intervention of several CAM techniques and products commonly used by cancer patients and survivors has been established in some cancer populations. Efficacy of some CAM techniques and products in reducing stress has been documented as well as stress-related symptoms in patients with cancer such as mindfulness-based stress reduction, yoga, Tai Chi Chuan, acupuncture, energy-based techniques, and physical activity. Much of the research limitations include small study samples and variety of intervention length and content. Efficacy and safety of many CAM techniques and some herbs and vitamin B and D supplements need to be confirmed in further studies using scientific methodology. Several complementary and alternative medicine therapies could be integrated into standard cancer care to ameliorate cancer-related stress.

Epstein-Barr virus infection is common in inflamed gastrointestinal mucosa.

BACKGROUND AND AIMS: Epstein-Barr virus (EBV) is present in the malignant epithelial cells of 10% of all gastric adenocarcinomas; however, localization of the virus in normal gastrointestinal mucosa is largely unexplored. In the present study, we measured EBV DNA and localized viral gene products in gastritis specimens (n = 89), normal gastric and colonic mucosa (n = 14), Crohn's disease (n = 9), and ulcerative colitis (n = 11) tissues. METHODS: A battery of sensitive and specific quantitative polymerase chain reactions targeted six disparate regions of the EBV genome: BamH1 W, EBNA1, LMP1, LMP2, BZLF1, and EBER1. EBV infection was localized by EBV-encoded RNA (EBER) in situ hybridization and by immunohistochemical stains for viral latent proteins LMP1 and LMP2 and for viral lytic proteins BMRF1 and BZLF1. B lymphocytes were identified using CD20 immunostains. RESULTS: EBV DNA was essentially undetectable in normal gastric mucosa but was present in 46% of gastritis lesions, 44% of normal colonic mucosa, 55% of Crohn's disease, and 64% of ulcerative colitis samples. Levels of EBV DNA exceeded what would be expected based on the numbers of B lymphocytes in inflamed tissues, suggesting that EBV is preferentially localized to inflammatory gastrointestinal lesions. Histochemical staining revealed EBER expression in lymphoid cells of some PCR-positive lesions. The viral lytic viral proteins, BMRF1 and BZLF1, were expressed in lymphoid cells of two ulcerative colitis tissues, both of which had relatively high viral loads by quantitative PCR. CONCLUSION: EBV-infected lymphocytes are frequently present in inflamed gastric and colonic mucosa. Active viral replication in some lesions raises the possibility of virus-related perpetuation of gastrointestinal inflammation.

Preventive intervention for anxious preschoolers and their parents: strengthening early emotional development.

The high prevalence and early onset of anxiety disorders have inspired innovative prevention efforts targeting young at-risk children. With parent-child prevention models showing success for older children and adolescents, the goal of this study was to evaluate a parent-child indicated preventive intervention for preschoolers with mild to moderate anxiety symptoms. Sixteen children (ages 3-5) and at least one of their parents participated in Strengthening Early Emotional Development (SEED), a new 10-week intervention with concurrent groups for parents and children. Outcome measures included clinician-rated and parent-rated assessments of anxiety symptoms, as well as measures of emotion knowledge, parent anxiety, and parental attitudes about children's anxiety. Participation in SEED was associated with reduced child anxiety symptoms and improved emotion understanding skills. Parents reported decreases in their own anxiety, along with attitudes reflecting enhanced confidence in their children's ability to cope with anxiety. Reductions in child and parent anxiety were maintained at 3-month follow-up. Findings suggest that a parent-child cognitive-behavioral preventive intervention may hold promise for young children with mild to moderate anxiety. Improvements in parent anxiety and parental attitudes may support the utility of intervening with parents. Fostering increased willingness to encourage their children to engage in new and anxiety-provoking situations may help promote continued mastery of new skills and successful coping with anxiety.

Ionizing radiation: the good, the bad, and the ugly.

Skin changes caused by ionizing radiation have been scientifically documented since 1902. Ionizing radiation is a widely accepted form of treatment for various types of cancer. Despite the technological advances, radiation skin injury remains a significant problem. This injury, often referred to as radiation dermatitis, occurs in about 95% of patients receiving radiation therapy for cancer, and ranges in severity from mild erythema to moist desquamation and ulceration. Ionizing radiation is not only a concern for cancer patients, but also a public health concern because of the potential for and reality of a nuclear and/or radiological event. Recently, the United States has increased efforts to develop medical countermeasures to protect against radiation toxicities from acts of bioterrorism, as well as cancer treatment. Management of radiation dermatitis would improve the therapeutic benefit of radiation therapy for cancer and potentially the mortality expected in any "dirty bomb" attack. Currently, there is no effective treatment to prevent or mitigate radiation skin injury. This review summarizes "the good, the bad, and the ugly" of current and evolving knowledge regarding mechanisms of and treatments for radiation skin injury.

Treating adolescents with social anxiety disorder in schools.

As is evident from the topic of this issue, schools can play an important role in addressing the unmet mental health needs of youth. Social anxiety disorder is particularly suited to being treated in the school setting. This article describes an empirically supported school-based intervention for social anxiety disorder, skills for academic and social success, and provides specific strategies to school counselors, teachers and community practitioners for implementing these methods. This article focuses on practical approaches for working with socially anxious adolescents in the school setting and how to increase awareness of social anxiety with parents and school personnel.

Ginger (Zingiber officinale) reduces acute chemotherapy-induced nausea: a URCC CCOP study of 576 patients.

PURPOSE: Despite the widespread use of antiemetics, nausea continues to be reported by over 70% of patients receiving chemotherapy. METHODS: In this double blind, multicenter trial, we randomly assigned 744 cancer patients to four arms: 1) placebo, 2) 0.5 g ginger, 3) 1.0 g ginger, or 4) 1.5 g ginger. Nausea occurrence and severity were assessed at a baseline cycle and the two following cycles during which patients were taking their assigned study medication. All patients received a 5-HT(3) receptor antagonist antiemetic on Day 1 of all cycles. Patients took three capsules of ginger (250 mg) or placebo twice daily for 6 days starting 3 days before the first day of chemotherapy. Patients reported the severity of nausea on a 7-point rating scale ("1" = "Not at all Nauseated" and "7" = "Extremely Nauseated") for Days 1-4 of each cycle. The primary outcomes were to determine the dose and efficacy of ginger at reducing the severity of chemotherapy-induced nausea on Day 1 of chemotherapy. RESULTS: A total of 576 patients were included in final analysis (91% female, mean age = 53). Mixed model analyses demonstrated that all doses of ginger significantly reduced acute nausea severity compared to placebo on Day 1 of chemotherapy (p = 0.003). The largest reduction in nausea intensity occurred with 0.5 g and 1.0 g of ginger (p = 0.017 and p = 0.036, respectively). Anticipatory nausea was a key factor in acute chemotherapy-induced nausea (p < 0.0001). CONCLUSIONS: Ginger supplementation at a daily dose of 0.5 g-1.0 g significantly aids in reduction of the severity of acute chemotherapy-induced nausea in adult cancer patients.

Treatment of Nausea and Vomiting During Chemotherapy.

Nausea and vomiting are two of the most troubling side effects patients experience during chemotherapy. While newly available treatments have improved our ability to manage nausea and vomiting, anticipatory and delayed nausea and vomiting are still a major problem for patients receiving chemotherapy. Many cancer patients will delay or refuse future chemotherapy treatments and contemplate stopping chemotherapy altogether because of their fear of experiencing further nausea and vomiting. The purpose of this article is to provide an overview of the patho-psychophysiology of chemotherapy-induced nausea and vomiting and the recommended guidelines for treatment.