Determinants of CD4 cell count decline after treatment interruption

Patients who had started HAART (Highly Active Anti-Retroviral Treatment) under previous aggressive DHHS guidelines (1997) underwent a life-long continuous HAART that was associated with many short term as well as long term complications. Many interventions attempted to reduce those complications including intermittent treatment also called pulse therapy. Many studies were done to study the determinants of rate of fall in CD4 count after interruption as this data would help guide treatment interruptions. The data set used here was a part of a cohort study taking place at the Johns Hopkins AIDS service since January 1984, in which the data were collected both prospectively and retrospectively. The patients in this data set consisted of 47 patients receiving via pulse therapy with the aim of reducing the long-term complications. ^ The aim of this project was to study the impact of virologic and immunologic factors on the rate of CD4 loss after treatment interruption. The exposure variables under investigation included CD4 cell count and viral load at treatment initiation. The rates of change of CD4 cell count after treatment interruption was estimated from observed data using advanced longitudinal data analysis methods (i.e., linear mixed model). Using random effects accounted for repeated measures of CD4 per person after treatment interruption. The regression coefficient estimates from the model was then used to produce subject specific rates of CD4 change accounting for group trends in change. The exposure variables of interest were age, race, and gender, CD4 cell counts and HIV RNA levels at HAART initiation. ^ The rate of fall of CD4 count did not depend on CD4 cell count or viral load at initiation of treatment. Thus these factors may not be used to determine who can have a chance of successful treatment interruption. CD4 and viral load were again studied by t-tests and ANOVA test after grouping based on medians and quartiles to see any difference in means of rate of CD4 fall after interruption. There was no significant difference between the groups suggesting that there was no association between rate of fall of CD4 after treatment interruption and above mentioned exposure variables. ^

Impact of real time polymerase chain reaction technology on the therapeutic approach to treatment of staphylococcal infections

Can the early identification of the species of staphylococcus responsible for infection by the use of Real Time PCR technology influence the approach to the treatment of these infections? ^ This study was a retrospective cohort study in which two groups of patients were compared. The first group, ‘Physician Aware’ consisted of patients in whom physicians were informed of specific staphylococcal species and antibiotic sensitivity (using RT-PCR) at the time of notification of the gram stain. The second group, ‘Physician Unaware’ consisted of patients in whom treating physicians received the same information 24–72 hours later as a result of blood culture and antibiotic sensitivity determination. ^ The approach to treatment was compared between ‘Physician Aware’ and ‘Physician Unaware’ groups for three different microbiological diagnoses—namely MRSA, MSSA and no-SA (or coagulase negative Staphylococcus). ^ For a diagnosis of MRSA, the mean time interval to the initiation of Vancomycin therapy was 1.08 hours in the ‘Physician Aware’ group as compared to 5.84 hours in the ‘Physician Unaware’ group (p=0.34). ^ For a diagnosis of MSSA, the mean time interval to the initiation of specific anti-MSSA therapy with Nafcillin was 5.18 hours in the ‘Physician Aware’ group as compared to 49.8 hours in the ‘Physician Unaware’ group (p=0.007). Also, for the same diagnosis, the mean duration of empiric therapy in the ‘Physician Aware’ group was 19.68 hours as compared to 80.75 hours in the ‘Physician Unaware’ group (p=0.003) ^ For a diagnosis of no-SA or coagulase negative staphylococcus, the mean duration of empiric therapy was 35.65 hours in the ‘Physician Aware’ group as compared to 44.38 hours in the ‘Physician Unaware’ group (p=0.07). However, when treatment was considered a categorical variable and after exclusion of all cases where anti-MRS therapy was used for unrelated conditions, only 20 of 72 cases in the ‘Physician Aware’ group received treatment as compared to 48 of 106 cases in the ‘Physician Unaware’ group. ^ Conclusions. Earlier diagnosis of MRSA may not alter final treatment outcomes. However, earlier identification may lead to the earlier institution of measures to limit the spread of infection. The early diagnosis of MSSA infection, does lead to treatment with specific antibiotic therapy at an earlier stage of treatment. Also, the duration of empiric therapy is greatly reduced by early diagnosis. The early diagnosis of coagulase negative staphylococcal infection leads to a lower rate of unnecessary treatment for these infections as they are commonly considered contaminants. ^

A qualitative and quantitative assessment of cancer patients' perceptions of barriers to treatment

This study examined barriers that cancer patients experience in obtaining treatment. The principal aim of the study was to conduct a comprehensive quantitative and qualitative assessment of barriers to cancer treatment for Texas cancer patients. The three specific aims of the study were to: (1) conduct a review and critique of published and unpublished research on barriers to cancer treatment; (2) conduct focus groups for the qualitative assessment of cancer patients' perceived barriers to cancer treatment; and (3) survey a representative sample of cancer patients regarding perceived barriers to treatment. The study was guided by the Aday and Andersen access framework of predisposing, enabling, and need determinants of care-seeking.^ To address the first specific aim, a total of 732 abstracts were examined, from which 154 articles were selected for review. Of these 154 articles, 57 that related directly to research on barriers to cancer treatment were chosen for subsequent analysis. Criteria were applied to each article to evaluate the strength of the study design, sampling and measurement procedures. The major barriers that were consistently documented to influence whether or not cancer patients sought or continued required treatment included problems with communication between the patient and provider, lack of information on side effects, the cost of treatment and associated difficulties in obtaining and maintaining insurance coverage, and the absence of formal and informal networks of social support. Access barriers were generally greater for older, minority women, and patients of lower socioeconomic status.^ To address the second specific aim, a total of eight focus groups (n = 44) were conducted across the State of Texas with cancer patients identified by the Texas Community Oncology Network, American Cancer Society, and community health centers. One important finding was that cost is the greatest hurdle that patients face. Another finding was that with the health care/insurance crisis, an increasing number of physicians are working with their patients to develop individually-tailored payment plans. For people in rural areas, travel to treatment sites is a major barrier due to the travel costs as well as work time forfeited by patients and their family members. A third major finding was the patients' family and church play important roles in providing social and emotional support for cancer patients.^ To address the third aim, a total of 910 cancer patients were surveyed during October and November, 1993. Approximately 65% of the cancer patients responded to the survey. The findings showed that the major barriers to treatment included costs of medications and diagnostic tests, transportation, lack of social support, problems understanding the written information regarding their disease as well as losing coverage or having higher premiums or copayments once they were diagnosed (particularly among blacks).^ Significant differences in reported barriers were found between racial groups. The minority respondents (i.e., blacks and Hispanics) tended to experience more barriers to treatment compared to the white respondents. More specifically, Hispanics were more likely to report transportation as a barrier to treatment than both white and blacks. Future research is needed to better understand the problems that minority cancer patients experience in receiving treatment. (Abstract shortened by UMI.) ^

A Pre-Clinical Assessment of Minocycline for Treatment of Chronic Neuropathic Pain after Spinal Cord Injury

Patients living with a spinal cord injury (SCI) often develop chronic neuropathic pain (CNP). Unfortunately, the clinically approved, current standard of treatment, gabapentin, only provides temporary pain relief. This treatment can cause numerous adverse side effects that negatively affect the daily lives of SCI patients. There is a great need for alternative, effective treatments for SCI-dependent CNP. Minocycline, an FDA-approved antibiotic, has been widely prescribed for the treatment of acne for several decades. However, recent studies demonstrate that minocycline has neuroprotective properties in several pre-clinical rodent models of CNS trauma and disease. Pre-clinical studies also show that short-term minocycline treatment can prevent the onset of CNP when delivered during the acute stage of SCI and can also transiently attenuate established CNP when delivered briefly during the chronic stage of SCI. However, the potential to abolish or attenuate CNP via long-term administration of minocycline after SCI is unknown. The purpose of this study was to investigate the potential efficacy and safety of long-term administration of minocycline to abolish or attenuate CNP following SCI. A severe spinal contusion injury was administered on adult, male, Sprague-Dawley rats. At day 29 post-injury, I initiated a three-week treatment regimen of daily administration with minocycline (50 mg/kg), gabapentin (50 mg/kg) or saline. The minocycline treatment group demonstrated a significant reduction in below-level mechanical allodynia and above- level hyperalgesia while on their treatment regimen. After a ten-day washout period of minocycline, the animals continued to demonstrate a significant reduction in below-level mechanical allodynia and above-level hyperalgesia. However, minocycline-treated animals exhibited abnormal weight gain and hepatotoxicity compared to gapabentin-treated or vehicle-treated subjects.The results support previous findings that minocycline can attenuate CNP after SCI and suggested that minocycline can also attenuate CNP via long-term delivery of minocycline after SCI (36). The data also suggested that minocycline had a lasting effect at reducing pain symptoms. However, the adverse side effects of long-term use of minocycline should not be ignored in the rodent model. Gabapentin treatment caused a significant decrease in below-level mechanical allodynia and below-level hyperalgesia during the treatment regimen. Because gabapentin treatment has an analgesic effect at the concentration I administered, the results were expected. However, I also found that gabapentin-treated animals demonstrated a sustained reduction in pain ten days after treatment withdrawal. This result was unexpected because gabapentin has a short half-life of 1.7 hours in rodents and previous studies have demonstrated that pre-drug pain levels return shortly after withdrawal of treatment. Additionally, the gabapentin-treated animals demonstrated a significant and sustained increase in rearing events compared with all other treatment groups which suggested that gabapentin treatment was not only capable of reducing pain long-term but may also significantly improve trunk stability or improve motor function recovery.

Malignant spinal cord compression: prospective study of delays in referral and treatment

Objectives: To examine the delay in presentation, diagnosis, and treatment of malignant spinal cord compression and to define the effect of this delay on motor and bladder function at the time of treatment.

Examining the Impact of Child Psychologists' Stigmatization of Parents on Treatment Outcomes Through a Developmental Lens

The purpose of this paper is to examine how child psychologists' specialized training inhuman development may make them more prone to stigmatize the parents of their young clients. The stigmatization of parents may lead to fewer parents seeking treatment for their children and to poorer treatment outcomes for those who work with a child psychologist. The process of stigmatization is summarized to provide context for the method through which parents receive stigma. A commonly used theory of child development, Erik Erikson's stages of ego development, is outlined to provide background on how child psychologists may interpret and evaluate a child'sdevelopment. Child psychologists' may identify parenting practices that seem to hinder or stunt children's emotional development, which would make the psychologist more aptto stigmatize and isolate parents from the treatment process. To demonstrate the unique ways in which a child psychologist may stigmatize parents of children at different developmental stages two case studies are included. Finally, a theoretical model of treatment is described that may be more inclusive, and less stigmatizing of parents. This model outlines how the parents' concerns about and observations of their children should be validated and reflected in the treatment process. This treatment modality would allow for child psychologists to more actively involve parents in treatment and provide more education and support around their children's unique emotional development needs. Through this treatment model and child psychologists' awareness of and attempts to reduce the stigmatization of parents, treatment outcomes for young clients may improve.

Energy consumption in an urban wastewater treatment plant: the case of Murcia Region (Spain)

Of all the costs associated with the operation and maintenance of wastewater treatment plants (WWTPs), those associated with energy use tend to be the most significant. From this point of view, it is hence logical that energy efficiency and saving strategies should be one of the current focuses of debate amongst those involved with the management of WWTPs. The present study's objective is to determine the correlation between size and energy consumption for a WWTP. To this end, 90 WWTPs currently in service were analysed and their energetic impact quantified in terms of kWh/m3 of water treated. The results obtained demonstrate that energy consumption ratio increases as the size of WWTPs decreases, either in terms of treatment volume or population equivalent served.

Secondary prevention of renal and cardiovascular disease: Results of a renal and cardiovascular treatment program in an Australian aboriginal community

Australian Aborigines are experiencing an epidemic of renal and cardiovascular disease. In late 1995 we introduced a treatment program into the Tiwi community, which has a three- to fivefold increase in death rates and a recent annual incidence of treated ESRD of 2760 per million. Eligible for treatment were people with hypertension, diabetics with micro or overt albuminuria, and all people with overt albuminuria. Treatment centered around use of perindopril (Coversyl, Servier), with other agents added to reach BP goals; attempts to control glucose and lipid levels; and health education. Thirty percent of the adult population, or 267 people, were enrolled, with a mean follow up of 3.39 yr. Clinical parameters were followed every 6 mo, and rates of terminal endpoints were compared with those of 327 historical controls matched for baseline disease severity, followed in the pretreatment program era. There was a dramatic reduction in BP in the treatment group, which was sustained through 3 yr of treatment. Albuminuria and GFR stabilized or improved. Rates of natural deaths were reduced by an estimated 50% (P = 0.012); renal deaths were reduced by 57% (P = 0.038); and nonrenal deaths by 46% (P = 0.085). Survival benefit was suggested at all levels of overt albuminuria, and regardless of diabetes status, baseline BP, or prior administration of angiotensin converting enzyme inhibitors (ACEI). No significant benefit was apparent among people without overt albuminuria, nor among those with GFR less than 60 ml/min. An estimated 13 renal deaths and 10 nonrenal deaths were prevented, with the number-needed-to-treat to avoid one terminal event of only 11.6. Falling deaths and renal failure in the whole community support these estimates. The program was extremely cost-effective. Programs like this should be introduced to all high-risk communities as a matter of urgency.

Effect of periodontal treatment on the serum antibody levels to heat shock proteins

We have shown previously that both humoral and cellular immune responses to heat shock protein 60 (HSP60) are elevated in chronic periodontitis patients compared with non-diseased subjects. The aim of the present study was to determine whether periodontal treatment could influence the level of serum antibodies to human HSP60 and Porphyromonas gingivalis GroEL, a bacterial homologue of human HSP60. Sera were obtained from 21 patients with moderate to advanced chronic periodontitis at the baseline examination and again after completion of treatment. Antibody levels were determined using an enzyme-linked immunosorbent assay. The mean anti-P. gingivalis GroEL antibody levels were down-regulated significantly by periodontal treatment when recombinant P. gingivalis GroEL was used as an antigen, whereas antibody levels to P. gingivalis GroEL-specific peptide were significantly elevated following successful periodontal therapy. The mean level of anti-human HSP60 antibody remained unchanged although individual levels of antibody either increased or decreased after periodontal treatment, suggesting that synthesis of these antibodies might be regulated independently during the course of periodontal infection. Although their regulatory mechanisms in chronic infection are not understood, further study would provide insight not only into the role of these antibodies in the pathogenesis of periodontitis but also into the possible link between periodontitis and systemic diseases such as coronary heart disease.

Modelling the population cost-effectiveness of current and evidence-based optimal treatment for anxiety disorders

Background. The present paper describes a component of a large Population cost-effectiveness study that aimed to identify the averted burden and economic efficiency of current and optimal treatment for the major mental disorders. This paper reports on the findings for the anxiety disorders (panic disorder/agoraphobia, social phobia, generalized anxiety disorder, post-traumatic stress disorder and obsessive-compulsive disorder). Method. Outcome was calculated as averted 'years lived with disability' (YLD), a population summary measure of disability burden. Costs were the direct health care costs in 1997-8 Australian dollars. The cost per YLD averted (efficiency) was calculated for those already in contact with the health system for a mental health problem (current care) and for a hypothetical optimal care package of evidence-based treatment for this same group. Data sources included the Australian National Survey of Mental Health and Well-being and published treatment effects and unit costs. Results. Current coverage was around 40% for most disorders with the exception of social phobia at 21%. Receipt of interventions consistent with evidence-based care ranged from 32% of those in contact with services for social phobia to 64% for post-traumatic stress disorder. The cost of this care was estimated at $400 million, resulting in a cost per YLD averted ranging from $7761 for generalized anxiety disorder to $34 389 for panic/agoraphobia. Under optimal care, costs remained similar but health gains were increased substantially, reducing the cost per YLD to < $20 000 for all disorders. Conclusions. Evidence-based care for anxiety disorders would produce greater population health gain at a similar cost to that of current care, resulting in a substantial increase in the cost-effectiveness of treatment.

Prospective study of men's psychological and decision-related adjustment after treatment for localized prostate cancer

Objectives. To undertake a prospective longitudinal study to assess psychological and decision-related distress after the diagnosis of localized prostate cancer. Methods. A total of I 11 men (93% response rate) with localized prostate cancer were recruited from outpatient urology clinics and urologists' private practices. More than one half (56%) elected to undergo radical prostatectomy, 19% underwent external beam radiotherapy, and 25% chose watchful waiting. Men completed self-report measures before treatment and 2 and 12 months after treatment. The measures used included the University of California, Los Angeles, Prostate Cancer Index, International Prostate Symptom Score, Impact of Events Scale, Constructed Meaning Scale, Satisfaction with Life Scale, Health Care Orientation subscale, and Decisional Conflict Scale. Results. No statistically significant differences were found by medical treatment group in the psychological and decision-related adjustment at baseline or with time. Men who were undecided about their treatment choice had greater decisional conflict and a more negative healthcare orientation, but were not more psychologically distressed, compared with men who had decided. At diagnosis, 63% of men had high decision-related distress, and this persisted for 42% of men 12 months after treatment, despite high satisfaction with their treatment choice. At diagnosis, low-to-moderate psychological distress was most common, with distress decreasing after treatment. The overall quality of life was similar to community norms. Conclusions. The results of our study indicated that men who were undecided about what treatment to receive experienced greater decision-related distress. The final treatment choice was not related to psychological distress about prostate cancer. Psychological and decision-related distress decreased with time, independent of treatment modality. Interventions should target decision-related distress for all men and in-depth psychological support for those who experience ongoing difficulties. (C) 2004 Elsevier Inc.

Chemoradiation therapy is effective for the palliative treatment of malignant dysphagia

Between 1993 and 2001, 106 patients with esophageal cancer were reviewed at a multidisciplinary clinic and treated with palliative intent by chemoradiation therapy. This study assesses the palliative benefit on dysphagia and documents the toxicity of this treatment. The study population comprised 72 men and 34 women with a median age of 69 years. Patients were treated with a median radiation dose of 35 Gy in 15 fractions with a concurrent single course of 5 FU-based chemotherapy. Dysphagia was measured at the beginning and completion of treatment and at monthly intervals until death, using a modified DeMeester (4-point) score. Treatment was well tolerated, with only 5% of patients failing to complete therapy. The treatment-related mortality was 6%. The median survival for the study population was 7 months. The median baseline score at presentation was 2 (difficulty with soft food). Following treatment, 49% of patients were assessed as having a dysphagia score of 0 (no dysphagia). Seventy-eight per cent had an improvement of at least one grade in their dysphagia score after treatment. Only 14% of patients showed no improvement with treatment. Fifty-one per cent maintained improved swallowing until the time of last follow-up or death. This single-institution study shows that chemoradiation therapy administered for the palliation of malignant dysphagia is well tolerated and produces a sustainable normalization in swallowing for almost half of all patients.

Effect of periodontal treatment on the C-reactive protein and proinflammatory cytokine levels in Japanese periodontitis patients

Background: Recent epidemiological studies have shown that individuals with periodontitis have a significantly increased risk of developing coronary heart disease. In addition to conventional risk factors, chronic infection and subsequent production of systemic inflammatory markers may be associated with this increased risk. Objectives: The aim of the present study was to determine whether the presence of chronic periodontitis and subsequent periodontal treatment could influence the serum levels of C-reactive protein (CRP), interleukin-6 and tumor necrosis factor-alpha (TNF-alpha) in a Japanese population. Methods: Sera were obtained from 24 patients with moderate to advanced periodontitis at the baseline examination and at reassessment after completion of treatment. As a control, sera were also obtained from 21 subjects without periodontitis. High-sensitivity CRP (hs-CRP) was measured using nephelometry with a latex particle-enhanced immunoassay and interleukin-6 and TNF-alpha were determined by sensitive enzyme-linked immunosorbent assay. Results: The levels of hs-CRP and interleukin-6 in the sera of this Japanese population seemed to be much lower than those reported in other populations. TNF-alpha on the other hand, demonstrated similar levels between this Japanese and other populations. Periodontal status demonstrated a significant improvement in all patients following treatment. There was a trend toward higher hs-CRP levels in patients at baseline compared with control subjects. Hs-CRP level tended to decrease with improvement of the periodontal condition following treatment and approached that of control subjects, although this decline was not statistically significant. interleukin-6 and TNF-alpha levels did not change following periodontal treatment. Furthermore, there was no difference in the serum levels of these inflammatory cytokines between patients either at baseline or at reassessment and control subjects. Conclusions: In this pilot study, we were unable to show that periodontal disease significantly affects the serum levels of systemic inflammatory markers. However, this does not necessarily mean that periodontitis does not contribute to the total burden of inflammation as there was a tendency for hs-CRP to decrease following successful periodontal treatment. Large-scale studies are clearly needed to determine the impact of periodontal disease on systemic inflammation.

Nutrient partitioning during treatment of tuberculosis: gain in body fat mass but not in protein mass

Background: Tuberculosis is an important cause of wasting. The functional consequences of wasting and recovery may depend on the distribution of lost and gained nutrient stores between protein and fat masses. Objective: The goal was to study nutrient partitioning, ie, the proportion of weight change attributable to changes in fat mass (FM) versus protein mass (PM), during anti mycobacterial treatment. Design: Body-composition measures were made of 21 men and 9 women with pulmonary tuberculosis at baseline and after 1 and 6 mo of treatment. All subjects underwent dual-energy X-ray absorptiometry and deuterium bromide dilution tests, and a four-compartment model of FM, total body water (TBW), bone minerals (BM), and PM was derived. The ratio of PM to FM at any time was expressed as the energy content (p-ratio). Changes in the p-ratio were related to disease severity as measured by radiologic criteria. Results: Patients gained 10% in body weight (P < 0.001) from baseline to month 6. This was mainly due to a 44% gain in FM (P < 0.001); PM, BM, and TBW did not change significantly. Results were similar in men and women. The p-ratio decreased from baseline to month 1 and then fell further by month 6. Radiologic disease severity was not correlated with changes in the p-ratio. Conclusions: Microbiological cure of tuberculosis does not restore PM within 6 mo, despite a strong anabolic response. Change in the p-ratio is a suitable parameter for use in studying the effect of disease on body composition because it allows transformation of such effects into a normal distribution across a wide range of baseline proportion between fat and protein mass.

Language outcomes subsequent to treatment of brainstem tumour in childhood

While the occurrence and management of brainstem tumours in children would not traditionally indicate potential direct structural impact on classical language centres, recent theories have implicated some involvement of the brainstem in a functional language and cognitive neural loop between the cerebellum and the cerebral hemispheres. Thus, the present paper explored the impact of treatment for brainstem tumour on the general and high-level language abilities of six children treated for brainstem tumour, in addition to phonological awareness skills. Group analysis revealed that children treated for brainstem tumour demonstrated intact language and phonological awareness abilities in comparison to an age- and gender-matched control group. Individual analysis revealed only one of six children treated for brainstem tumour revealed evidence of language disturbances, with an additional child demonstrating an isolated mildly reduced score on one phonological awareness task. Language deficits identified in a child treated with a combination of both radiotherapy and chemotherapy were noted in the high-level language area of lexical generation. Findings highlighted that no overt language disturbances were evident in children treated for brainstem tumour. However, further analysis into higher-level language skills in the present study indicated that both general and high-level language abilities require long-term monitoring in this population.