Benefit related assessment of treatment need among institutionalised elderly people

It has been assumed that improved oral health leads to a better quality of life for elderly people. It is, however, difficult to assess the benefit of oral health care, especially dental treatment in terms of life quality. The normative assessment, based solely on clinical diagnosis, often leads to an overestimation of the true need for treatment, especially among the ‘frail elderly’, some of whom do not want treatment, either because there is no perceived need or expressed demand. Others are very ill, and some in such a poor mental condition that they can not express any demand for treatment, and would probably not benefit from treatment e.g. new dentures. The realistic treatment need is an attempt to assess the true need for treatment in relation to the benefit provided. It is a combination of the normative need, the self-perceived need, and the expressed demand for treatment, and takes into account the mental and physical state of the individual, as well as ethical considerations.     

Subset Selection of an Almost Best Treatment

A generalized goal using subset selection is discussed for the location parameter case. This goal is to select a non-empty subset from a set of k (k ≥ 2) treatments that contains at least one ε-best treatment with confidence level P*. For a set of treatments an ε-best treatment is defined as a treatment with location parameter on a distance less than or equal to ε(ε ≥o) from the best treatment, where best is defined as largest value of the location parameter. The efficiency of subset selection of an ε-best treatment relative to subset selection of the best treatment is investigated and is computed for some values of k and the confidence level for the Normal case as well as for the Logistic case.     

Overview of surgical treatments for breast cancer-related lymphedema

Breast cancer-related upper extremity lymphedema is an unsolved iatrogenic complication with a reported incidence ranging from 9 to 41 percent. The increase in volume and recurrent cellulitis of the affected limb cause both physical and mental distress to many breast cancer survivors. However, postmastectomy lymphedema has received little attention, and no curative treatment is available. Conservative treatment with decongestive therapy has been the primary choice for lymphedema treatment, but it is cumbersome and has limited benefits. To date, there is no consensus on surgical procedure and protocol. However, refinements in microsurgical techniques and improved examination devices may lead to the establishment of a standard surgical treatment for lymphedema. This review of surgical procedures for the treatment of postmastectomy lymphedema focuses on microsurgical lymphovenous shunt operations and discusses current issues in surgical treatment and the need for uniform treatment standards.     

婴幼儿呼吸道合胞病毒感染的治疗

呼吸道合胞病毒(respiratory syncytial virus RSV)是引起婴幼儿毛细支气管炎最重要的病原体。其主要临床表现为喘息。部分患儿可出现反复喘息发作而发展为哮喘。对RSV感染尚无特效治疗药物,仍然以支持对症治疗为主,目前的研究热点是中西医结合治疗,反义基因治疗,高渗盐水雾化吸入治疗等。     

Assessing exposure-time treatment effect heterogeneity in stepped-wedge cluster randomized trials

A stepped-wedge cluster randomized trial (CRT) is a unidirectional crossover study in which timings of treatment initiation for clusters are randomized. Because the timing of treatment initiation is different for each cluster, an emerging question is whether the treatment effect depends on the exposure time, namely, the time duration since the initiation of treatment. Existing approaches for assessing exposure-time treatment effect heterogeneity either assume a parametric functional form of exposure time or model the exposure time as a categorical variable, in which case the number of parameters increases with the number of exposure-time periods, leading to a potential loss in efficiency. In this article, we propose a new model formulation for assessing treatment effect heterogeneity over exposure time. Rather than a categorical term for each level of exposure time, the proposed model includes a random effect to represent varying treatment effects by exposure time. This allows for pooling information across exposure-time periods and may result in more precise average and exposure-time-specific treatment effect estimates. In addition, we develop an accompanying permutation test for the variance component of the heterogeneous treatment effect parameters. We conduct simulation studies to compare the proposed model and permutation test to alternative methods to elucidate their finite-sample operating characteristics, and to generate practical guidance on model choices for assessing exposure-time treatment effect heterogeneity in stepped-wedge CRTs.     

A proposal for the use of advance directives in the treatment of incompetent mentally ill persons

[M]y question is how these patients while competent might be able to give their own informed consent to treatment, despite being both unwilling and incompetent to do so when treatment is to be begun, thereby reducing the need to relax the dangerousness criteria for involuntary commitment. It is uncontroversial that the dangerousness requirement would be too restrictive for all treatment of mental illness. When competent patients voluntarily seek and/or accept treatment for their mental illness, neither public policy nor medical practice restricts treatment to those patients judged to be dangerous. Instead, criteria should be and generally are comparable to those for the treatment of physical illness -- whether the patient is ill, in this case mentally ill, and likely to benefit from treatment. Through use of advance directives, it would be possible for mentally ill persons who are currently refusing treatment to give prior consent, while competent and with their disease in remission, to treatment at a later time when they are incompetent, have become noncompliant, and are refusing treatment. My proposal is certainly not entirely novel, since others have made similar proposals under the heading of Ulysses contracts and voluntary commitment contracts. Addressing briefly some of the criticisms of these earlier proposals will bring out one fundamental difference between them and my proposal here for a new use of advance directives -- whether the patient must then be incompetent when the contract or directive made earlier is later invoked -- a difference I shall argue strongly favors my proposal.     

Robustness of Treatment Planning for Electrochemotherapy of Deep-Seated Tumors

Treatment of cutaneous and subcutaneous tumors with electrochemotherapy has become a regular clinical method, while treatment of deep-seated tumors is still at an early stage of development. We present a method for preparing a dedicated patient-specific, computer-optimized treatment plan for electrochemotherapy of deep-seated tumors based on medical images. The treatment plan takes into account the patient’s anatomy, tissue conductivity changes during electroporation and the constraints of the pulse generator. Analysis of the robustness of a treatment plan made with this method shows that the effectiveness of the treatment is not affected significantly by small single errors in electrode positioning. However, when many errors occur simultaneously, the resulting drop in effectiveness is larger, which means that it is necessary to be as accurate as possible in electrode positioning. The largest effect on treatment effectiveness stems from uncertainties in dielectric properties and electroporation thresholds of treated tumors and surrounding tissues, which emphasizes the need for more accurate measurements and more research. The presented methods for treatment planning and robustness analysis allow quantification of the treatment reproducibility and enable the setting of suitable safety margins to improve the likelihood of successful treatment of deep-seated tumors by electrochemotherapy.     

FROM MEDICAL RATIONING TO RATIONALIZING THE USE OF HUMAN RESOURCES FOR AIDS CARE AND TREATMENT IN AFRICA: A CASE FOR TASK SHIFTING

With a global commitment to scaling up AIDS care and treatment in resource‐poor settings for some of the most HIV‐affected countries in Africa, availability of antiretroviral treatment is no longer the principal obstacle to expanding access to treatment. A shortage of trained healthcare personnel to initiate treatment and manage patients represents a more challenging barrier to offering life‐saving treatment to all patients in need. Physician‐centered treatment policies accentuate this challenge. Despite evidence that task shifting for nurse‐centered AIDS patient care is effective and can alleviate severe physician shortages that currently obstruct treatment scale‐up, political commitment and policy action to support task shifting models of care has been slow to absent. In this paper we review the evidence in support of task shifting for AIDS treatment in Africa and argue that continued policy inaction amounts to unwarranted healthcare rationing and as such is ethically untenable.     

Assessing the Effect of the Best Treatment. A Non-parametric Inference Problem

For patients of a certain type, a number of treatments are available. The effect of each such treatment is assumed to be described by a shift model; it is, however, admitted that there may be an interaction between patient and treatment, meaning in particular that the treatment which is best for one patient is not necessarily best for another. The problem is the following: if each patient is given the treatment which is optimal for that particular patient, will this produce a significant effect and, if so, how large is the effect?     

口腔内入路行髁突高位骨折复位固定的临床效果

目的：探讨采用口腔内入路手术复位固定方法治疗下颌骨髁突颈骨折患者的临床效果。方法：将我院收治的20例下颌骨髁突颈骨折患者均使用口腔内入路手术复位固定方法治疗,将患者的骨折片与升支后缘骨块进行手术复位固定,并于原手术切口行回植,重建患者的下颌关节。结果：治疗后咬合关系异常者1例,开口范围限制者0例,关节疼痛者1例,均少于治疗前均为20例;治疗后关节间隙缩小者1例,髁突骨折块形状异常者1例,均少于治疗前均为20例。治疗后髁突稳定者19例,多于治疗前的1例。结论：髁突骨折治疗手术各有优缺点,采用口腔内入路手术复位固定方法治疗髁突高位骨折患者,虽然手术操作难度大,但能较好地克服了术后患者外部皮肤瘢痕明显的问题,有利于保护患者面部神经,提高患者治疗质量水平,值得临床上推广与进一步研究。     

Methods for evaluating response to treatment in adult acute leukemia

The criteria for evaluating response to treatment for patients with adult acute leukemia are objective, quantitative, and effective. The first objective of treatment is to achieve a complete clinical and hematological remission, since in the absence of such response the disease has a rapidly progressive and inevitably fatal outcome. Logistic regression analysis and the generation of models for predicting the probability of response for each patient have proven to be extremely useful techniques for evaluating new candidates for front-line treatment in acute leukemia. In prospective tests, such modeling procedures have proven to predict accurately for response. It is evident that this methodology will be highly effective for selecting treatment for individual patients and for detecting improved treatments for patients who respond poorly to conventional treatment. For patients who achieve complete remission, the duration of that remission can also be evaluated by logistic regression analysis. Variables which predict for duration of remission have proven to be different from those variables which predict for probability of response. In addition, variables which predict for prolonged remission--that is, beyond 2 and 3 years--have proven to be different from variables which predict for relapse in the first year of remission. Therefore, the models which estimate risk of relapse per unit of time at risk should prove most valuable for evaluating not only the choice of treatments to be used during remission, but the duration of treatment and the strategy of treatment, that is, whether intensive treatment or low-dose intermittent treatment should be chosen. Finally, the demonstration that a significant fraction of the patients in complete remission will have long term disease-free and treatment-free survival makes the identification of such patients even more important. Evaluation of innovative higher-risk strategies for treatment of the patient in remission should be offered primarily to patients who have a low probability of having already been cured with conventional treatment. Thus, the rapid evolution of effective treatment for adult acute leukemia over the last 15 years has necessitated the development of more precise and more effective methods for evaluating the effects of those treatments on patients with this disease.     

Radiotherapy in the treatment of Graves ophthalmopathy—to do it or not?

To the objective of this study is to evaluate the role and toxicity of radiotherapy in the treatment of Graves ophthalmopathy. In the years 2000–2003, 121 patients with malignant exophthalmos were treated with radiotherapy of the retrobulbar area to the total dose of 20 Gy in ten fractions with a 6 MeV photon beam. The treatment was performed by the team of the Clinic of Oncology of the Jagiellonian University Medical College in Cracow. The radiotherapy was preceded by intravenous steroid therapy: methylprednisolone acetate administered at the dose of 2 g/week for four consecutive weeks. The highest efficacy, expressed as improvement of all ocular symptoms, was observed for the combined treatment. Female and non-diabetic patients responded positively to the combined treatment. Radiotherapy combined with steroid therapy in the treatment of Graves ophthalmopathy seems to be an effective treatment for strictly defined indications. In the treatment of Graves–Basedow disease, radiotherapy is a well-tolerated treatment modality. Diabetes is a factor that worsens prognosis in Graves ophthalmopathy and female sex is a favourable factor for this condition.     

The effect of treatment delay on time-to-recovery in the presence of unobserved heterogeneity

We study the effect of delaying treatment in the presence of (unobserved) heterogeneity. In a homogeneous population and assuming a proportional treatment effect, a treatment delay period will result in notably lower cumulative recovery percentages. We show in theoretical scenarios using frailty models that if the population is heterogeneous, the effect of a delay period is much smaller. This can be explained by the selection process that is induced by the frailty. Patient groups that start treatment later have already undergone more selection. The marginal hazard ratio for the treatment will act differently in such a more homogeneous patient group. We further discuss modeling approaches for estimating the effect of treatment delay in the presence of heterogeneity, and compare their performance in a simulation study. The conventional Cox model that fails to account for heterogeneity overestimates the effect of treatment delay. Including interaction terms between treatment and starting time of treatment or between treatment and follow up time gave no improvement. Estimating a frailty term can improve the estimation, but is sensitive to misspecification of the frailty distribution. Therefore, multiple frailty distributions should be used and the results should be compared using the Akaike Information Criterion. Non-parametric estimation of the cumulative recovery percentages can be considered if the dataset contains sufficient long term follow up for each of the delay strategies. The methods are demonstrated on a motivating application evaluating the effect of delaying the start of treatment with assisted reproductive techniques on time-to-pregnancy in couples with unexplained subfertility.     

慢性粒细胞白血病耐药机制及治疗策略

慢性粒细胞白血病是一类造血干细胞的恶性克隆性疾病,ph染色体是其特征性细胞遗传学标志,即t(9;22)(q34;ql1),存在BCR/ABL融合基因,现阶段造血干细胞移植是当前最有希望治愈CML的疗法,但受年龄、配型等限制,易发生移植物抗宿主病;复发率较高;传统的化疗、干扰素治疗也有副作用,因此,通过信号传导抑制剂抑制BCR-ABL酪氨酸激酶活性,从而阻止一系列信号传导来治疗CML是一个比较好的治疗方法,伊马替尼是一种酪氨酸激酶抑制剂是治疗慢性粒细胞白血病的靶向治疗药物,治疗疗效显著,但是并不能根治慢性粒细胞白血病,需要长期服药,一些患者出现耐药,导致治疗无效或复发。因此,寻求新的治疗方案至关重要。本文就慢性粒细胞白血病的耐药机制及治疗策略做一综述。     

The role of surgery in the treatment of malignant melanoma

Surgical interventions have important role in the treatment of all stages of malignant melanoma. Surgery is the primary treatment of localized cutaneous melanoma. Excision of the primary tumor makes it possible to set up the histological diagnosis and to determine pathological prognostic factors. Appropriate surgical margin is important for local disease control. Sentinel lymph node biopsy with detailed histological examination has gained prominent importance for correct histological staging and for determining adjuvant oncological treatment. Surgery is the primary treatment of isolated regional metastases. Surgical methods also have a role in the palliative management of distant metastatic melanoma. In the present review the most important issues of the surgical treatment of malignant melanoma have been discussed in detail.     

Modelling the impact of fexinidazole use on human African trypanosomiasis (HAT) transmission in the Democratic Republic of the Congo

Gambiense human African trypanosomiasis is a deadly disease that has been declining in incidence since the start of the Century, primarily due to increased screening, diagnosis and treatment of infected people. The main treatment regimen currently in use requires a lumbar puncture as part of the diagnostic process to determine disease stage and hospital admission for drug administration. Fexinidazole is a new oral treatment for stage 1 and non-severe stage 2 human African trypanosomiasis. The World Health Organization has recently incorporated fexinidazole into its treatment guidelines for human African trypanosomiasis. The treatment does not require hospital admission or a lumbar puncture for all patients, which is likely to ease access for patients; however, it does require concomitant food intake, which is likely to reduce adherence. Here, we use a mathematical model calibrated to case and screening data from Mushie territory, in the Democratic Republic of the Congo, to explore the potential negative impact of poor compliance to an oral treatment, and potential gains to be made from increases in the rate at which patients seek treatment. We find that reductions in compliance in treatment of stage 1 cases are projected to result in the largest increase in further transmission of the disease, with failing to cure stage 2 cases also posing a smaller concern. Reductions in compliance may be offset by increases in the rate at which cases are passively detected. Efforts should therefore be made to ensure good adherence for stage 1 patients to treatment with fexinidazole and to improve access to care.     

Fighting polymicrobial biofilms in bacterial vaginosis

Bacterial vaginosis (BV) is the most common cause of vaginal discharge and is often associated with other health consequences mainly in pregnant women. BV is described by an imbalance in the vaginal microbiota where strictly and facultative anaerobic bacteria outgrow the lactic acid- and hydrogen peroxide-producing Lactobacillus species. The species involved in BV are capable to grow and form a polymicrobial biofilm in the vaginal epithelium. The treatment of BV is usually performed using broad-spectrum antibiotics, including metronidazole and clindamycin. However, these conventional treatments are associated with high recurrence rates. The BV polymicrobial biofilm may have an important role on the treatment outcome and is accounted as one of the factors for treatment failure. Other possible reasons for treatment failure include the presence of species resistant to antibiotics or the chance of reinfection after treatment. Therefore, novel strategies to increase the rates of treatment have been studied namely the use of probiotics and prebiotics, acidifying agents, antiseptics, plant-based products, vaginal microbiota transplantation, and phage endolysins. Although some of them are still in an initial phase of development with very preliminary results, they show great perspectives for application. In this review, we aimed to study the role of the polymicrobial nature of BV in treatment failure and explore a few alternatives for treatment.     

Run-Reversal Equilibrium for Clinical Trial Randomization

In this paper, we describe a new restricted randomization method called run-reversal equilibrium (RRE), which is a Nash equilibrium of a game where (1) the clinical trial statistician chooses a sequence of medical treatments, and (2) clinical investigators make treatment predictions. RRE randomization counteracts how each investigator could observe treatment histories in order to forecast upcoming treatments. Computation of a run-reversal equilibrium reflects how the treatment history at a particular site is imperfectly correlated with the treatment imbalance for the overall trial. An attractive feature of RRE randomization is that treatment imbalance follows a random walk at each site, while treatment balance is tightly constrained and regularly restored for the overall trial. Less predictable and therefore more scientifically valid experiments can be facilitated by run-reversal equilibrium for multi-site clinical trials.     

Patient navigation pathway and barriers to treatment seeking in cancer in India: A qualitative inquiry

Cancer is a leading cause of mortality worldwide. Early diagnosis and treatment of cancer may curb the growing burden of the disease. Understanding cancer patients’ navigation pathways for seeking treatment is important in order to facilitate early diagnosis and treatment. With this background we conducted a hospital-based cross-sectional study comprising 68 randomly selected cancer inpatients in a tertiary cancer specialty hospital in Odisha, India, to explore the treatment-seeking pathways of the cancer patients and the barriers and enablers in seeking treatment. Financial constraint is one of the major reasons for the delay in accessing treatment, even when patients are suspected of or diagnosed with cancer. Low awareness of the presenting signs and symptoms of cancer and limited knowledge of the availability of cancer diagnosis and treatment facilities are major factors contributing to delay. Family and friends’ support is found to be the major enabling factor toward seeking treatment. Generation of awareness of cancer among the general population and primary-care practitioners – including those in alternative systems of medicine – is important. Information on diagnostic and treatment services appears to be a felt need.