Is increased screening and early antiretroviral treatment for HIV-1 worth the investment? An analysis of the public health and economic impact of improvement in the UK.

OBJECTIVES: Early treatment of HIV-1 infection at all CD4 levels has demonstrated clinical and public health benefits. This analysis examined the costs, health outcomes, and cost-effectiveness of increased HIV-1 screening and early treatment initiation in the UK. METHODS: A Markov model followed theoretical cohorts of men who have sex with men (MSM), heterosexuals, and people who inject drugs (PWID) with initially undiagnosed HIV-1 infection over their remaining lifetimes. The analysis examined increased HIV-1 screening (resulting in 10-50% improvements in diagnosis rates) versus current screening in sexual health services (SHS) and other settings, with all individuals initiating treatment within 3 months of diagnosis. Health status was modelled by viral load and CD4 cell count as individuals progressed to diagnosis and treatment. Individuals accrued quality-adjusted life-years (QALYs), incurred costs for screening and HIV-related clinical management, and were at risk of transmitting HIV-1 infection to their partners. Input parameter data were taken primarily from UK-specific published sources. All outcomes were discounted at 3.5% annually. RESULTS: The model estimated that increased screening and early treatment resulted in fewer onward HIV transmissions, more QALYs, and higher total costs. For SHS, incremental cost-effectiveness ratios (ICERs) for heterosexuals (~£22 000/QALY gained) were within typical UK willingness-to-pay thresholds and were well below these thresholds for MSM (~£9500/QALY gained) and PWID (~£6500/QALY gained). Sensitivity analysis showed that model results were robust. CONCLUSIONS: Increased HIV-1 screening and early treatment initiation may be a cost-effective strategy to reduce HIV transmission and improve health for MSM, heterosexuals, and PWID in the UK.

Family Functioning and Suicidal Ideation/Behaviour in Adolescents: a Pilot Study

Objective: The main aim of this study was to explore the associations between specific aspects of family functioning and adolescent suicidal ideation/behaviour. Method: Participants were 87 high school students (43 male and 44 female) aged between 14 and 16 years of age. They completed a questionnaire measuring various aspects of family functioning and suicidal ideation/behaviour. The specific dimensions of family functioning assessed were: connection; psychological control and behavioural regulation in the parent-adolescent relationship; family conflict and family structure. Results: The results of t-test and chi-square analyses indicated that adolescents who reported suicidal ideation or behaviour in the previous year experienced lower levels of connection and regulation and higher levels of conflict and psychological control in the parent-child relationship than non-suicidal adolescents. Family structure and interparental conflict were not significantly associated with suicidal ideation/behaviour. Conclusions: The quality of relationships between adolescents and both of their parents may be important in distinguishing South African adolescents with recent suicidal ideation/behaviour from non-suicidal

Do shrimp-allergic individuals tolerate shrimp-derived glucosamine?

BACKGROUND: There is concern that shrimp-allergic individuals may react to glucosamine-containing products as shrimp shells are a major source of glucosamine used for human consumption. OBJECTIVE: The purpose of this study was to determine whether shrimp-allergic individuals can tolerate therapeutic doses of glucosamine. METHODS: Subjects with a history of shrimp allergy were recruited and tested for both shrimp reactivity via a prick skin test and shrimp-specific IgE by an ImmunoCAP assay. Fifteen subjects with positive skin tests to shrimp and an ImmunoCAP class level of two or greater were selected for a double-blind placebo-controlled food challenge (DBPCFC) using glucosamine-chondroitin tablets containing 1,500 mg of synthetically produced (control) or shrimp-derived glucosamine. Immediate reactions, including changes in peak flow and blood pressure, and delayed reactions (up to 24 h post-challenge) via questionnaire were noted and assessed. RESULTS: All subjects tolerated 1,500 mg of both shrimp-derived or synthetic glucosamine without incident of an immediate hypersensitivity response. Peak flows and blood pressures remained constant, and no subject had symptoms of a delayed reaction 24 h later. CONCLUSION: This study demonstrates that glucosamine supplements from specific manufacturers do not contain clinically relevant levels of shrimp allergen and therefore appear to pose no threat to shrimp-allergic individuals.

An esophagobronchial fistula caused by an unusual foreign body in the esophagus leading to mediastinitis with fatal outcome.

An 8(10)/(12) year old girl with infantile cerebral paresis (ICP), severe mental retardation and seizure disorder was admitted to the intensive care unit (ICU) with clinical signs of aspiration and died ten days later. Final diagnosis was esophagobronchial fistula caused by a foreign body in the esophagus provoking aspiration pneumonia, mediastinitis and respiratory distress syndrome (ARDS). The foreign body was found to be part of a plastic toy. The clinical relevance of aspiration in mentally retarded children and the peculiar nature of the foreign body impacted in the esophagus in this case are discussed. We conclude that in cases of aspiration pneumonia in mentally retarded children the presence of unusual foreign bodies should be suspected.

[Treatment of extreme tumour pain with morphine and s-ketamine A case report of an 11-year old girl]. / Therapie extremer Tumorschmerzen mit Morphin und (S)-Ketamin. Falldarstellung eines 11-jährigen Mädchens.

We are reporting on the case of an 11-year old girl with a malignant tumour. The extreme pain throughout the body could not be treated by conventional methods. By intravenous application of a morphine and s-ketamine mixture we were able to achieve a very effective analgesic result. Apart from the opiate effect of the morphine the decisive factor was the NMDA-antagonism of the s-ketamine. The latter suppresses central sensitisation and chronic pain and reduces or even prevents the development of opioid tolerance. It was possible to use smaller opiate doses more effectively, thus reducing the side effects of the pain therapy. Under associated whole-body thermochemotherapy the girl experienced general pain relief and we were able to return to conventional therapy with a fentanyl plaster.

[Latex allergy in childhood--case reports]. / Latexallergie im Kindesalter--Kasuistik.

Three cases of latex anaphylaxis occurring during surgery are reported. Sudden cardiorespiratory collapse 40 to 90 minutes after induction of anaesthesia was treated with oxygen, crystalloid solution, adrenaline and methylprednisolone. Laboratory findings showed markedly elevated antibodies against latex postoperatively. All three patients had anorectal malformations. As children with malformations have to be operated on in early childhood, they have a high risk of developing antibodies against latex. Primary prophylaxis requires a general avoidance of latex products in children with malformations from the time of birth on.

Allergen immunotherapy.

Allergen immunotherapy has been used since the early 1900's for the treatment of allergic syndromes. The efficacy of immunotherapy for the treatment of anaphylaxis caused by the sting of the Hymenoptera class of insects, allergic rhinoconjunctivitis, and the allergic component of bronchial asthma has been clearly demonstrated in numerous well-designed, placebo-controlled trials. Many recent advances in our understanding of the cellular and molecular basis of the allergic response have permitted the development of innovative experimental approaches that very likely will improve the control of the allergic response in the future.

Hypersensitivity pneumonitis: a comprehensive review.

Hypersensitivity pneumonitis is a dynamic and heterogeneous group of diseases resulting from inhalational exposure to a variety of organic and inorganic dusts. In the United States, it has predominantly been considered an occupational disease, such as in farmer's lung, bagassosis, and in the plastics and paint industry with isocyanate exposure. In Japan, however, the most common exposure to antigen has been associated with the home environment. All susceptible patient populations are at potential risk to develop this disease under appropriate antigen exposure. The clinical course can be acute, subacute, or chronic depending on the nature of the antigen and the circumstances under which exposure occurs. If unrecognized, any stage of disease has the potential to progress to endstage pulmonary fibrosis. Proper antigen identification and avoidance requires that the physician be keenly aware of its existence and the importance of the detailed occupational and home environmental history. Without a high degree of suspicion, this disease can be easily overlooked and misdiagnosed as another type of inflammatory lung disease. Although the immunologic mechanisms mediating this illness are complex and poorly understood, strict avoidance of the provocative antigen is required for optimal long-term outcome.

Patients' perceptions and responses to procedural pain: results from Thunder Project II.

BACKGROUND: Little is known about the painfulness of procedures commonly performed in acute and critical care settings. OBJECTIVE: To describe pain associated with turning, wound drain removal, tracheal suctioning, femoral catheter removal, placement of a central venous catheter, and nonburn wound dressing change and frequency of use of analgesics during procedures. METHODS: A comparative, descriptive design was used. Numeric rating scales were used to measure pain intensity and procedural distress; word lists, to measure pain quality. RESULTS: Data were obtained from 6201 patients: 176 younger than 18 years and 5957 adults. Mean pain intensity scores for turning and tracheal suctioning were 2.80 and 3.00, respectively (scale, 0-5), for 4- to 7-year-olds and 52.0 and 28.1 (scale, 0-100) for 8- to 12-year-olds. For adolescents, mean pain intensity scores for wound dressing change, turning, tracheal suctioning, and wound drain removal were 5 to 7 (scale, 0-10); mean procedural distress scores were 4.83 to 6.00 (scale, 0-10). In adults, mean pain intensity scores for all procedures were 2.65 to 4.93 (scale, 0-10); mean procedural distress scores were 1.89 to 3.47 (scale, 0-10). The most painful and distressing procedures were turning for adults and wound care for adolescents. Procedural pain was often described as sharp, stinging, stabbing, shooting, and awful. Less than 20% of patients received opiates before procedures. CONCLUSIONS: Procedural pain varies considerably and is procedure specific. Because procedures are performed so often, more individualized attention to preparation for and control of procedural pain is warranted.

Immunotherapy for food allergy.

Food allergy is an important cause of life-threatening hypersensitivity reactions. Avoidance of allergenic foods is the only method of prevention that currently is available for sensitized patients. This method of prevention is difficult and often impossible. With better characterization of allergens and better understanding of the immunologic mechanism, investigators have developed several therapeutic modalities that potentially are applicable to the treatment and prevention of food allergy. Therapeutic options currently under investigation include peptide immunotherapy, DNA immunization, immunization with immunostimulatory sequences, anti-IgE therapy, and genetic modification of foods. These exciting developments hold promise for the safe and effective treatment and prevention of food allergy in the next several years.

Commentary. Balancing sedation and analgesia in the critically ill.

The authors have presented a template for a systematic approach to comforting critically ill patients that can be modified to suit institutional preferences. In this algorithm, the cause of patient discomfort is sought with the priority given to pain and then to anxiety. Special attention is directed to the identification of correctable causes of pain and anxiety with application of nonpharmacologic techniques or medications to control patient discomfort. This step is followed by subsequent reassessment of the need for sedation or anxiolysis and titration or discontinuation of therapy as able. The benefits of protocol-driven care are becoming increasingly evident, and the authors believe the algorithm outlined here provides a rational and practical approach to patient management. It also prompts the caregiver to reevaluate patients' needs and to keep to patients at target sedation levels. Doing so can promote cost effectiveness, reduce side effects caused by drugs, and decrease morbidity and ICU stay. Any treatment protocol or algorithm is simply a guide to therapy and cannot address every clinical situation. The importance of individualized care and physician or care team judgment must be emphasized.

Pain management. An organizational perspective.

To sustain optimal pain-relieving care for acutely and critically ill patients, organizations must have systems in place to support evidence-based interventions, facilitate expert practice in the area of pain management, and encourage ongoing communication among patients, families, and providers. The key to success may be to create an organizational culture that is supportive of all practitioners to use effectively the many therapeutic options available to manage pain. Although redesigning structures to support pain management care can be done with relative ease, altering the culture of the practice environment and the behavior of care providers may prove more challenging. Cultural changes occur slowly, but as the practice changes do take hold, so do the results. The steps to change an organizational culture around pain management include understanding the existing system and involving key formal and informal leaders. Most experts recommend not attacking the existing culture head-on but living the culture you are trying to create and understanding that the transformation is not going to take place overnight. The use of evidence-based collaborative practice and quality improvement models may be a key to improving the practice environment for pain management. Evidenced-based pain management practice combined with an organizational commitment to optimal pain management for all patients helps to create and sustain the environment to effect the change.

Translating research into practice. Implications of the Thunder Project II.

The Thunder Project II study described procedural pain in a variety of acute and critical care settings. The procedures studied were turning, tracheal suctioning, wound drain removal, nonburn wound dressing change, femoral sheath removal, and central venous catheter insertion. Turning had the highest mean pain intensity, whereas femoral sheath removal and central venous catheter insertion had the least pain intensity in adults. Nonwound dressing change had the highest pain intensity for teenagers. Pain occurred in procedures that are often repeated several times a day as well as in those that may be single events. There is a wide range of pain responses to any of these procedures; as a result, standardized and thoughtful pain, and distress assessments are warranted. Planning of care, including the use of preemptive analgesic interventions, needs to be individualized. Future studies are needed to describe patient responses to other commonly performed nursing procedures and to identify effective interventions for reducing procedural pain and distress.

Speaking the same language: improving evaluation of patient-focused outcomes using standardized terminology.

As the practice of medicine grows in complexity and the public calls for demonstrated value at decreased cost, the need for increasing effectiveness of both providing care and evaluating patient outcomes becomes paramount. This paper will demonstrate the success of utilizing a standardized taxonomy within an automated patient record to provide cues to clinicians regarding individual, patient-focused outcomes as well as timely evaluation of aggregated patient outcomes data. A case study will be used to illustrate dynamic evaluation of clinical outcomes following cardiac surgery.

Quality pain management outcomes: the power of place.

This study explores how an organization, as the context of care, influences nursing practice and a nursing-sensitive, quality health outcome-pain management. The results provide important insights into organizational patterns associated with favorable pain management-related outcomes as well as the congruence between and among subunits within the organization. Outcomes were most favorable on units where nurses had attitudes supportive of aggressive pain management and higher levels of coordination and discretion.

[Propofol for intubation of infants after halothane induction]. / Propofol zur Intubation bei Säuglingen nach Halothaneinleitung.

UNLABELLED: The unwanted side effects of muscle relaxants used for anaesthesia in the newborn and infants resulted in a search for alternatives to atraumatic intubation (IN). The study was aimed to investigate conditions of intubation, time of intubation as well as changes in systolic, mean and diastolic blood pressure (RRs/RRm/RRd) and heart rate (HR) under the use of propofol (P) after narcosis induction by mask. PATIENTS AND METHODS: The study was approved by the local ethics committee. The data was analysed from 100 infants aged between 4 days and 56 weeks (weight 2110-9230 g) in the ASA I and II groups (Group [Gr] A and B both with 50 patients). In both groups induction was performed inhalationally with halothane (1.5-2.0 vol%) and pure oxygen. After that propofol for intubation was applied in a dose of 2 mg/kg i.v. In Gr A blood pressure and heart rate were registered at three measuring points (MP): MP 1 = before P administration, MP 2 = after P, MP 3 = following intubation; in Gr B at MP 1 and MP 3. Additionally in Gr B the intubation time was recorded in seconds (t1 = time after P administration to beginning of IN, t2 = time after P administration to the end of the IN, t3 = t2-t1). In both groups the conditions of intubation were assessed (score 1--excellent, 2--good, 3--bad, 4--impossible intubation). RESULTS: The means of RRs/RRm/RRd/HR varied in Gr A at MP 2 by -11.20*/-9.18*/-8.58*/-3.52 mmHg/bpm and at MP 3 by -2.74/-2.26/-2.04/+5.46 mmHg/bpm in comparison to MP 1 (p < 0.05 = significant*). Compared to MP 1 in Gr B the mean values of RRs/RRm/RRd/HR varied at MP 3 by -0.89/+0.50/-0.80/+4.20* mmHg/bpm. T1 (mean, SD) was 10.88 +/- 3.52 seconds (s), t2 26.22 +/- 6.12 s, and t3 was therefore 15.78 +/- 6.28 s. Conditions of intubation were found to be excellent or good in both groups (Gr A and B [100 patients]: score 1 = 95x = 95%, score 2 = 5x = 5%). CONCLUSION: In the observation period, changes in heart rate stayed in the range of reference. In our opinion the excellent and good conditions for intubation, as well as the ultrashort drug-onset and intubation time demonstrate the good characteristics afforded by propofol to perform intubation in infancy.

Plasma c-erbB-2 levels in breast cancer patients: prognostic significance in predicting response to chemotherapy.

PURPOSE: To determine the significance of plasma c-erbB-2 levels to assess the extent of disease spread and to predict the response to chemotherapy in node-positive breast cancer patients. METHODS: We determined plasma levels of c-erbB-2 in 79 stages II and III breast cancer patients who received cyclophosphamide, methotrexate, and flourouracil (CMF)/cyclophosphamide, methotrexate, fluorouracil, vincristine, and prednisone (CMFVP) chemotherapy. All patients had a minimum follow-up of greater than 60 months or until disease recurrence. Plasma samples were obtained before and after chemotherapy. Plasma c-erbB-2 levels were quantified by enzyme-linked immunoassay. c-erbB-2 levels were analyzed in relation to the patients' axillary lymph node status, menopausal status, disease status, disease-free survival (DFS), and steroid receptor status of tumor. RESULTS: Plasma c-erbB-2 levels varied widely in breast cancer patients. In general, when all patients were included in the analyses, plasma c-erbB-2 levels before chemotherapy correlated significantly with the number of positive axillary lymph nodes and with postchemotherapy c-erbB-2 levels. No association was observed between pre- or postchemotherapy c-erbB-2 levels and other variables (patients' age at diagnosis, receptor status of the tumor, or disease status). The prognostic significance of different factors (ie, nodal status [one to three v > three positive nodes], menopausal status [pre- v postmenopausal women], estrogen receptor [ER] status [ER+ v ER-], and pre- and postchemotherapy c-erbB-2 levels) in predicting DFS was determined in all study patients. Among the variables examined, nodal status was the strongest predictor of DFS in these patients. The second most significant prognostic marker was postchemotherapy c-erbB-2 level. Prechemotherapy c-erbB-2 levels showed prognostic significance for DFS in a subset of breast cancer patients (ie, patients with > three positive nodes). Patients with greater than three positive lymph nodes and those with greater than 100 fmol/mL of plasma c-erbB-2 levels before therapy had significantly shorter DFS than did those patients with 100 fmol/mL or less c-erbB-2 levels. CONCLUSION: In breast cancer patients, determination of c-erbB-2 levels before therapy is an important biomarker to assess the extent of disease spread in the lymph nodes. Postchemotherapy c-erbB-2 levels are also a prognostic indicator for DFS in patients who receive chemotherapy. Finally, in a subgroup of patients with greater than three positive nodes, prechemotherapy c-erbB-2 levels are a prognostic marker for response of patients to standard chemotherapy.

[Serum cytokines and cytokine receptors in children after small or larger surgical interventions with halothane anesthesia]. / Zytokine und Zytokinrezeptoren im Serum von Kindern nach kleinen oder grösseren chirurgischen Eingriffen unter Halothan-Narkose.

Immune dysfunction or immune defect syndrome can result postoperatively. It is not yet clear what part is played by the operative trauma itself or by narcotics. To answer this question, 54 patients (ASA 1) aged between 4 and 16 were examined. In group I there were 28 patients with minor operations and in group II 26 patients with moderate ones. We chose halothan, N2O and O2 for inhalational anaesthesia for all patients, IL-6. TNF alpha, IL-IRA, IL-2R and sTNF-RII measuring times were preoperative directly postoperative and on the first and third postoperative days. In contrast to TNF-alpha, IL-6 showed itself in both groups to be an "early" immune parameter with trauma-related kinetics. IL-IRA increased in both groups with significant values on the first postoperative day. Trauma-related differences between the groups were apparent. sIL-2R was less pronounced, IL-6 and IL-IRA parameters proved to be sensitive indicators of operative trauma intensity. The differing IL-IRA kinetic after minor or moderate trauma indicates that narcotic effects may be manifested at cytokine receptor level. Monitoring of the presented parameters on the first and third postoperative days together with base data appears to be appropriate for determining perioperative immune reaction.