Negative Therapeutic Effect Research Articles

Towards international collaboration of clinical research networks for EMDR: the EMDR Pain Network Germany.

Eye Movement Desensitization and Reprocessing (EMDR) is an evidence-based treatment, primarily established for post-traumatic stress disorder (PTSD). While it is increasingly being applied to chronic pain, its efficacy in this area is not yet supported by the same level of evidence as that which exists for PTSD. Studies in this area often show heterogeneous results with small case numbers, and the potential side effects of EMDR in the treatment of chronic pain are not well understood. Systematic documentation of treatment effects, potential predictors of treatment response and non-response, and side effects is crucial for progress in this field. The primary aim is to establish a research framework to systematically investigate the delivery of EMDR therapies by outpatient clinicians in the field of pain. This study aims to provide a comprehensive analysis of treatment outcomes, side effects and determinants of treatment effectiveness, whether positive response or non-response. This framework will oversee the documentation and evaluation of EMDR interventions delivered in outpatient settings using an Embedded Continuous Cumulative Evaluation Design (ECCED). It will focus on detailed characterisation of positive and negative therapeutic effects. It will also identify and analyse prognostic factors that influence individual variability in response to treatment. Treatment materials, standardised assessments and an intervision platform for regular exchange will be provided. The establishment of the EMDR Pain Network Germany and an interdisciplinary scientific-clinical platform is essential to promote clinical exchange and understanding of the effects of EMDR in pain therapy. This platform offers standardised treatment protocols, an online data collection system with anonymised data, comprehensive baseline assessments and an intervision platform for regular exchange. The knowledge gained is intended to personalise future therapies and serve as a basis for large randomised clinical trials.

Predicting the effectiveness of organ-preserving treatment of choroidal melanoma using optical coherence tomography data

This study was conducted to identify OCT signs that adversely affect the outcome of organ-preserving CM treatment. OCT scan images of 30 patients who underwent organ-preserving treatment and were under observation were selected for this study. Brachytherapy (BT) as monotherapy was performed in 27 patients (in 2 cases - twice, and in 1 case - three times), in one patient - in combination with the previous transpupillary thermotherapy (TTT). Multiple TTT (4 sessions within 4 months) as monotherapy were performed in 2 patients. In 9 cases, a single organ-preserving treatment (BT - 6 patients, TTT - 3 patients) was ineffective. In these cases, the effectiveness of the first stage of organ-preserving treatment was taken into account. Seven signs of an unfavorable prognosis of the performed treatment were identified by analyzis of tomograms and statistical processing of the obtained data. These signs include: the presence of intraretinal edema, detachment of the neuroepithelium (NED) over the tumor, including with a break in the photoreceptors, accumulation of transudate over the tumor, the presence of large cysts, intraretinal cavities and NED near the tumor (secondary retinal detachment). A combination of three or more signs were observed in all cases of inefficiency of the first stage of treatment. Most often, intraretinal edema and NED over the tumor were combined with the accumulation of subretinal transudate and NED near the tumor. The presence of 6 or all 7 signs took place in cases of a negative therapeutic effect after local destruction. When planning organ-preserving CM treatment, in addition to biometric parameters, it is necessary to pay special attention to the identification of such morphological signs as NED over and near the tumor, accumulation of transudate under the NED, the presence of intraretinal edema, large intraretinal cysts and cavities.

Nocebo effects in the treatment of endometriosis.

The current approach to treating endometriosis is often inadequate or intolerable for many patients. Until more effective therapies are available, we should aim to maximize the effectiveness of our current options. Optimization may be possible by reducing nocebo effects, which are the negative therapeutic effects not directly caused by a treatment. Awareness of these effects, how they arise, and the factors influencing them, is invaluable if we aim to limit their magnitude. The unique nature of endometriosis diagnosis and management is especially prone to nocebo effects due to multiple factors, including diagnostic delays, feelings of invalidation, social transmission of expectations, and persistent symptoms despite numerous treatments. This commentary discusses the origins of these effects in people with endometriosis, methods of limiting nocebo effects, and future research directions.Lay summaryThe term ‘nocebo’ describes the undesirable effects of a medication or treatment that patients may experience which are not directly caused by the treatment (e.g. tiredness from a sugar pill). These arise from pre-existing expectations toward a treatment and are influenced by multiple external factors, including past experiences, online media, personal beliefs, and personality factors. Endometriosis is a disease characterized by cells like those from the inside of the uterus growing outside of the uterus. The complex nature of endometriosis diagnosis and management creates an environment where nocebo effects may affect treatment outcomes. We may be able to limit nocebo effects through awareness and simple actions that strengthen patient–doctor relationships. Effective therapeutic relationships with doctors are crucial in limiting negative expectations and are established through empathy, honesty, and support. Therapeutic relationships built on trust may allow healthcare providers to address negative expectations, nocebo effects, and the misinformation affecting endometriosis management.

Thymosin Beta 4 Is Involved in the Development of Electroacupuncture Tolerance.

Background: Electroacupuncture (EA) tolerance, a negative therapeutic effect, is a gradual decline in antinociception because of its repeated or prolonged use. This study aims to explore the role of thymosin beta 4 (Tβ4), having neuro-protection properties, in EA tolerance (EAT).Methods: Rats were treated with EA once daily for eight consecutive days to establish EAT, effect of Tβ4 on the development of EAT was determined through microinjection of Tβ4 antibody and siRNA into the cerebroventricle. The mRNA and protein expression profiles of Tβ4, opioid peptides (enkephalin, dynorphin and endorphin), and anti-opioid peptides (cholecystokinin octapeptide, CCK-8 and orphanin FQ, OFQ), and mu opioid receptor (MOR) and CCK B receptor (CCKBR) in the brain areas (hypothalamus, thalamus, cortex, midbrain and medulla) were characterized after Tβ4 siRNA was administered.Results: Tβ4 levels were increased at day 1, 4, and 8 and negatively correlated with the changes of tail flick latency in all areas. Tβ4 antibody and siRNA postponed EAT. Tβ4 siRNA caused decreased Tβ4 levels in all areas, which resulted in increased enkephalin, dynorphin, endorphin and MOR levels in most measured areas during repeated EA, but unchanged OFQ, CCK-8, and CCKBR levels in most measured areas. Tβ4 levels were negatively correlated with enkephalin, dynorphin, endorphin, or MOR levels in all areas except medulla, while positively correlated with OFQ and CCK-8 levels in some areas.Conclusion: These results confirmed Tβ4 facilitates EAT probably through negatively changing endogenous opioid peptides and their receptors and positively influencing anti-opioid peptides in the central nervous system.

The role of clinical experience, diagnosis, and theoretical orientation in the treatment of posttraumatic and dissociative disorders: A vignette and survey investigation

ABSTRACTControversy exists regarding the merits of exposure-based treatments for posttraumatic stress disorder (PTSD) versus a phased approach when prominent dissociative symptoms are present. The first aim of this study was to examine the degree to which diagnosing dissociation in two traumatized patients’ vignettes influenced clinicians’ preference for phase-oriented treatment and whether clinicians’ treatment experience contributed to their treatment preference. The second aim was to assess the extent to which participants had observed traumatized patients worsen when treated with exposure therapy or phase-oriented therapy and whether the theoretical orientation and treatment experience of the clinician were related to the observed deterioration. In the tradition of expert and practitioner surveys, 263 clinicians completed a survey of their diagnoses and treatment preferences for two vignettes and their treatment experience, theoretical orientation, and observations of patients’ deterioration. When a marked degree of dissociation was noted in the PTSD vignette, respondents favored phased approaches regardless of the diagnosis given. Reports of having observed patient deterioration during both exposure and phased therapy were predicted by years of experience. Psychodynamic therapists reported more observations of worsening during exposure therapy than cognitive behavior therapy therapists. Clinical experience treating PTSD may heighten awareness of negative therapeutic effects, potentially because experienced clinicians have a lower threshold for detecting such effects and because they are referred more challenging cases.

“First do no harm” and the importance of prediction in oncology

Present cancer treatment strategies are based on the assumption that a therapy may work (“response”) or not work (“no-response”). However, the existing evidence suggests that current cancer treatment modalities may also have a cancer-promoting effect in part of the patients. In this paper, some relevant data are reviewed suggesting that surgery, irradiation, chemotherapy and immunotherapy can stimulate tumor growth / metastatic spread and decrease survival of patients in certain subgroups. Thus, results of cancer treatment may be improved by detection and use of biomarkers that correlate with positive or negative therapeutic effects. Small trials based on groups with differing biomarkers rather than large phase III trials may aid the development and efficacy testing of new anticancer drugs. Moreover, ignoring biomarkers that correlate with positive or negative therapeutic effect may not be compatible anymore with the ethical principle “First Do No Harm”.

Prescribing practices of clozapine in India: Results of a opinion survey of psychiatrists

Byline: Amresh. Shrivastava, Nilesh. Shah Sir, Clozapine has emerged as a gold standard for treatment resistant schizophrenia. It is also effective in a variety of clinical conditions. It is additionally approved for suicide in schizophrenia. However practice of clozapine therapy is complex due to its side effect profile, need for regular blood monitoring, continued clinical monitoring and requirements of logistical support system for the same. Indian conditions are diverse not only socio-economically but also in pattern of prescribing. Practice of psychiatry in India is therefore challenging. Internationally clozapine is a centrally monitored and guided therapy involving a number of agencies. The present report attempts to examine prescribing and monitoring practices of clozapine in Indian context. Clozapine is an atypical antipsychotic, which is credited to have the distinction of bringing in the second revolution in psychopharmacology. It has been main focus of management for treatment-resistant schizophrenia. It has also provided a probe for the biological mechanism of schizophrenia. Many patients became functional with clozapine therapy and have returned to college and work.[sup] [1] After several deaths due to agranulocytosis, the drug was approved with a condition of stringent blood monitoring, and this practice is strictly adhered to in each and every western countries. Clinical practice in India does not have the benefit of a centralized blood monitoring system. The present study is aimed to explore the prescribing practice of clozapine in this context. Serum level monitoring is also not available in routine clinical practice. These constrains may change the practice of clozapine therapy.[sup] [2],[3] The study was done using a specifically prepared semi- structured performa containing 32 items and the questionnaire circulated to about 500 psychiatrists in India. A sizable number of posting was done in urban areas besides metro cities and the survey was voluntary. The responses received were analyzed. A total of 117 responses were received in this study, 9.4% of the psychiatrists have reported using clozapine even before it was launched in Indian Market. Antipsychotic prescribing practices are influenced by several factors. Chong et al. noted that Japan had a high frequency of prescribing high doses and polypharmacy; Singapore had a high utilization of depot injections, while China had a higher prescription of clozapine. First-generation drugs were mainly for controlling aggressive behavior, while second-generation drugs were targeted at the alleviation of positive, negative psychotic symptoms as well as disruptive behavior in schizophrenia. The pattern of antipsychotic medication use varies in different countries and is likely to be influenced by the prevailing health-care system, the availability and cost of the drugs.[sup] [4] Most of the psychiatrists using clozapine have an experience of more than 10 years (51%, between 10 and 20 yrs; 28%> 20 years). In the present study, 50% doctors have been using clozapine because they had one more option, and only 28% doctors felt that the knowledge of efficacy has guided their clinical decision.[sup] [5] Further, 43% doctors felt that clozapine provides very good and excellent outcome. The majority opinion was that clozapine provided an efficacy from 40 to 70% in terms of symptom reduction. Switching to clozapine is recommended under strict monitoring with a definite washout period either on outpatient or on inpatient basis.[sup] [6] However, in this study, only 39% preferred stopping ongoing antipsychotic before starting clozapine. A majority of them used the gradual introduction method, 41% preferred to start clozapine gradually, while gradually withdrawing the existing antipsychotic. Eighty-four percent preferred to maintain patients on single drug clozapine as per best practices norm. …

Oncolytic Immunovirotherapy for Melanoma Using Vesicular Stomatitis Virus

Relatively little attention has been paid to the role of virotherapy in promoting antitumor immune responses. Here, we show that CD8+ T cells are critical for the efficacy of intratumoral vesicular stomatitis virus virotherapy and are induced against both virally encoded and tumor-associated immunodominant epitopes. We tested three separate immune interventions to increase the frequency/activity of activated antitumoral T cells. Depletion of Treg had a negative therapeutic effect because it relieved suppression of the antiviral immune response, leading to early viral clearance. In contrast, increasing the circulating levels of tumor antigen-specific T cells using adoptive T cell transfer therapy, in combination with intratumoral virotherapy, generated significantly improved therapy over either adoptive therapy or virotherapy alone. Moreover, the incorporation of a tumor-associated antigen within the oncolytic vesicular stomatitis virus increased the levels of activation of naïve T cells against the antigen, which translated into increased antitumor therapy. Therefore, our results show that strategies which enhance immune activation against tumor-associated antigens can also be used to enhance the efficacy of virotherapy.

Low-Level Laser Therapy after Molar Extraction

The aim of the study was to evaluate effect of the different frequencies of low-level laser radiation (diode 670 nm and Helium-Neon 632.8 nm) on the healing process after human molar extractions. Frequencies of 5 Hz, 292 Hz, and 9,000 Hz were used in experiments. Monitoring of secretory IgA and albumin level in saliva and changes in bone density were used as objective markers of biostimulatory effect. From the literature, it is known that if the alveolus is irradiated after extraction along with the lingual and buccal bony wall, faster coagulation, less postoperative discomfort, and quicker healing can be expected. Subjective evaluation of therapy was observed using a scale (from -, negative therapeutic effect, to ++++, excellent treatment effect). Changes of secretory immunoglobulin A (sIgA), albumin levels, and bone density were compared in a group of 150 patients (nonlaser therapy, 30 patients). Differences in levels of the saliva markers (sIgA and albumin) were found to be significant when comparing irradiated and nonirradiated groups, and in comparison with those groups irradiated by various modulatory frequencies. Significant differences were observed between the increase of sIgA res. albumin and subjective feelings during treatment. Bone density after extraction and 6 months after surgical treatment was examined using dental digital radiovisiography. No significant differences were detected between bone density in irradiated and nonirradiated groups, perhaps due to our therapy protocol. The low-level laser has no influence on the process of osseointegration. This effect was observed on fracture healing in rats using He-Ne laser radiation. We found no differences in the bone density when compared to the control group.

Transsexualism in a Klinefelter male: a case report

AbstractWe report a Klinefelter male who presents requesting gender reassignment surgery. There may be a predisposition to gender dysphoria in Klinefelter's Syndrome, and in the case we describe, the perception of his symptoms as being of biological origin coupled with the unavailability of gender reassignment surgery in the Republic of Ireland has had a negative therapeutic effect.

Discontinuation of Clonazepam After Long‐Term Treatment

Frequent unwanted side effects and development of tolerance are the main disadvantages of clonazepam (CZP) in long-term treatment of epileptic patients. A review of the literature shows that CZP tolerance more often appears in severe forms of childhood epilepsy (West and Lennox-Gastaut syndromes) than in other epileptic syndromes. We prospectively studied the consequences of CZP discontinuation in 40 consecutive children with difficult-to-treat epilepsies and multiple-drug therapy. The CZP was reduced stepwise in a variable daily reduction rate (0.003-0.16 mg/kg), while serum levels of the comedication were kept unchanged. In only three children (7.5%), CZP was believed to have had some antiepileptic effect; in 30 (75%) it had been ineffective, whereas in six (15%), a decrease in seizure frequency after CZP discontinuation even suggested a negative therapeutic effect. Discontinuation symptoms, mostly in the form of a transitory exacerbation of seizure frequency, occurred in 19 children (47.5%). These children had a significantly higher CZP dose and longer duration of treatment than did children without discontinuation symptoms, but there was no difference between the two groups related to the rate of CZP discontinuance.

ALS cerebrospinal fluid enhances human foetal astroglial cell proliferation in vitro.

Studies on the cerebrospinal fluid (CSF) of patients with amyotrophic lateral sclerosis (ALS) are relatively few and somewhat unclear. Recently, we were unable to demonstrate a cytotoxic effect of ALS sera on human central nervous system (CNS) cultures from 15 - 20 week old human foetuses, confirming the negative therapeutic effects obtained using plasma-exchange in affected patients[l]. We decided to study the effects of ALS-CSF on human foetal motor cortex in vitro. This tissue can grow in vitro in the presence of a standard tissue culture medium which contains 10% normal CSF and provides a sensitive assay for trophic factors and toxic substances of clinical relevance. ALS-CSF induces a significant glial cell proliferation in vitro. Indirect immunofluorescence techniques were used to identify the atroglial proliferating cells.

Social reinforcement in the modification of agoraphobia.

ALTHOUGH there is no convincing evidence from group outcome studies that psychotherapy is effective, 1 recent work 2 suggests that groups of patients so treated show both negative and positive change when compared to untreated controls. Those treated tend to be widely dispersed from improved to worsened, while untreated control subjects usually show slight improvement and cluster about the mean. The variability in outcome following psychotherapy appears to depend on therapist and to a lesser extent on patient characteristics. Thus the evidence suggests that behavioral change occurs during psychotherapy, but is masked in largesample statistical-outcome studies, where positive and negative therapeutic effects cancel out. An alternative research approach is the controlled study of the single case. This approach allows for detailed and sensitive investigation of the variables responsible for behavioral change in psychotherapy. Individualized and direct measures of pertinent symptomatic behaviors can be devised and monitored throughout an experimental therapy. The effect of a single therapeutic variable