Early Part Of Treatment Research Articles

Functional Outcome of Intra-articular Fractures of Distal Radius: ORIF with Locking Plate vs CRPP

Background: Distal radius fractures are common, costly, and increasing in incidence. Closed reduction and percutaneous K wires fixation and ORIF with locking plate fixation are two of the mostly used surgical treatments for dorsally displaced distal radius fractures. However, there is uncertainty which of these treatments is superior.
 Methods: This is a prospective study on 40 patients. Twenty patients had closed reduction and percutaneous pinning (CRPP) with K wires (Group A) and 20 patients had open reduction and internal fixation (ORIF) with locking plate and screws (Group B). Evaluation were done in the means of DASH scores and ROM of operated wrist on 1.5 months, three months and six months follow up period.
 Results: Though the overall functional outcome is comparatively better with Group B, the significant difference for most variables like DASH Scores, extension, supination and ulnar deviation were found at early part of treatment only. The flexion and radial deviation bear no significant outcomes at all intervals of evaluations. Superficial wound infection was more common in patients treated with K-wires but otherwise no difference in complication rates was noted.
 Conclusion: Locking plate fixation provided lower DASH scores and reduced total postoperative complications compared to CRPP group over six months follow-up period. However, these differences were significant in early part of treatment. Further research is required to better delineate the confirmation.

Predicting dropout in adolescents receiving therapy for depression

Objective: Therapy dropout is a common occurrence, especially in adolescence. This study investigated whether dropout could be predicted from a range of child, family, and treatment factors in a sample of adolescents receiving therapy for depression. Method: This study draws on data from 406 participants of the IMPACT study, a randomized controlled trial, investigating three types of therapy in the treatment of adolescent depression. Logistic regression was used to estimate the effects of predictors on the odds of dropout. Results: Few pre-treatment predictors of dropout were found, with the only significant predictors being older age, antisocial behaviour, and lower scores of verbal intelligence. Missed sessions and poorer therapeutic alliance early in treatment also predicted dropout. Most child and family factors investigated were not significantly associated with dropout. Conclusions: There may be little about depressed adolescents’ presentation prior to therapy starting that indicates their risk of dropout. However, within-treatment factors indicated that warning signs of dropout may be identifiable during the initial phase of therapy. Identifying and targeting early treatment indicators of dropout may provide possibilities for improving engagement.Clinical and methodological significance of this article: In the literature, a great deal of attention has been paid to child and family factors that predict therapy dropout, yet in this study, few pre-treatment characteristics were predictive of dropout. However, findings revealed possible warning signs of dropout in the early part of treatment, as poor therapeutic alliance and missed sessions were both found to be predictive of dropout. These findings call for therapists to be aware of such warning signs and clinical guidelines for managing cases at risk of dropout are warranted.

Clinico-pathological correlation and outcome analysis of disseminated histoplasmosis treated with conventional amphotericin B.

Introduction Disseminated histoplasmosis is a treatable common opportunistic infection in HIV infected people and not uncommon in others in a tropical country like India . The objective of our study was to evaluate clinical-pathological correlation and treatment outcome of disseminated histoplasmosis treated with conventional Amphotericin B in an endemic area. Material and methods This was a retrospective observational study of twenty-two cases of disseminated histoplasmosis admitted to a tertiary care hospital from January 2009 to December 2012 and treated with Amphotericin B followed by oral Itraconazole therapy for one year. Results of treatment outcome including relapse and mortality were analyzed in January 2014. Results Histoplasmosis was diagnosed in patients with advanced HIV (72%) illness with a mean CD4 count of 63.43/l. Tuberculosis and diabetes were other co-morbid illnesses and it was less common among immunocompetent patients (9%). Fifty percent of the patients presented with cutaneous lesions along with systemic manifestations while 27% had only mucocutaneous lesions. Adrenal histoplasmosis (18%) was common in HIV negative subjects. HIV positive patients showed excellent response to Amphotericin B followed by Itraconazole therapy. In 27% HIV positive patients, the disease manifested as IRIS (immune reconstitution inflammatory syndrome). Relapse was seen in 2(9%) patients. After one year of completion of therapy 16 patients were cured, 3 patients (13.6%) died in the early part of treatment and one was lost to follow up. Treatment response in HIV infected patients showed excellent results but long term maintenance itraconazole therapy was inevitable (12-32 months). Conclusions It is concluded that early diagnosis and treatment can prevent a fatal disease like disseminated histoplasmosis with conventional Amphotericin B followed by Itraconazole. Adrenal histoplasmosis was common among the HIV negative population. Extensive follow up is required to identify early relapse which may need further prolongation of therapy for cure.

Clinician and practice characteristics influencing delivery and outcomes of the early part of outpatient cognitive behavioural therapy for anorexia nervosa

AbstractCognitive-behavioural therapy (CBT) can be effective for anorexia nervosa. However, there is evidence that the delivery of treatments for the eating disorders is inconsistent. This study examined evidence that clinician characteristics and practice can influence the effective implementation of CBT. The participants were 100 qualified clinicians who routinely offered outpatient CBT to adults with anorexia nervosa. They completed a survey of their demographic characteristics, level of anxiety, clinical practice in CBT for anorexia nervosa, and beliefs about the relationship between weight gain and therapeutic alliance in the early part of such treatment. Greater reported levels of weight gain were associated with the use of manuals, early focus on weight gain as a target, structured eating, and a belief that weight gain precedes a good working alliance. Clinician anxiety and early focus on the therapeutic alliance rather than structured eating were associated with poorer outcomes. These conclusions need to be tested within clinical and research settings. However, they suggest that clinicians should be encouraged to use manual-based approaches when treating anorexia nervosa using CBT, as focusing on techniques might result in the best possible outcome in this early part of treatment.

A Novel and Efficient Induction Approach for Accelerated Differentiation and Rapid Hematopoietic Recovery in Acute Promyelocytic Leukemia (APL) Patients by Combining All-Trans Retinoic Acid (ATRA) with Granulocyte-Colony Stimulating Factor (G-CSF).

Background: Despite successful treatment with ATRA and chemotherapy (CT), nearly 10% of APL patients die during early part of treatment because of life threatening complications like bleeding, thrombosis, Retinoic Acid Syndrome (RAS) or infection. This number increases to >20% in most developing countries and presents significant challenge for clinicians. The goal is to develop therapy that rapidly corrects coagulopathy and also normalizes counts. Recent in-vitro data had suggested that G-CSF markedly and selectively stimulates the differentiating effect of ATRA in APL cells without increasing apoptosis. The objective of this pilot study was to evaluate the effect of G-CSF given along with ATRA during induction therapy in patients with APL.Patients and Methods: From 2003, 25 patients (ages 1 yr to 43 yrs; median 24 yrs) with APL ineligible for standard CT were treated on a pilot study with Oral CT: Prednisolone 40 mg/m2/d, Etoposide 50 mg/m2/d & 6TG 40 mg/m2/d (PET) for 21 days as induction therapy along with ATRA (45 mg/m2/d for 90 days) (Blood 2005; 106:900). On completion of oral CT, G-CSF (5 mg/kg/d) was added after day 25 to ATRA in 12 patients in view of persistent cytopenia (low ANC &/or platelets).Results: Patients received a median of 4 doses of G-CSF (range 2–12). The median ANC before starting G-CSF was 0.493 × 109/L (range 0.014–4.21) which increased to a median of 1.78 × 109/L (range 0.525–13.0) post G-CSF (> 1.0 × 109/L in 10/12 patients). Interestingly, platelet count which was < 50.0 × 109/L in 8/12 patients (median 44.15 × 109; range 12–178) prior to G-CSF, increased to > 100.0 × 109/L in all except one patient (median 177 × 109; range 64–357). Comparison of pre and post G-CSF cytogenetic status by FISH showed significant decrease in t (15; 17) positivity post ATRA-G-CSF exposure (78-0; 80-11; 54-10). In rest nine patients the bone marrow cytogenetic studies were done post G-CSF only. Complete morphological, cytogenetic and molecular remission was achieved in 9 patients (75%) at a median of 40 days. None of the patients developed RAS, bleeding or thrombotic complications. Presently all 12 patients continue to be in molecular remission at a median follow-up of 17 months (range 9–35 months).Conclusions: There is still a valuable role of single institutional trials in exploring innovative therapies in APL. Chemotherapy, ATRA and arsenic trioxide, all induce apoptosis which causes over expression of Annexin II, which in turn increases plasmin generation and thrombin generation. However, when G-CSF is used in combination with ATRA, neither proliferation arrest nor induction of apoptosis precedes the differentiation. Thus, use of G-CSF along with ATRA very early in therapy of APL may help to decrease or avoid the early life-threatening coagulation abnormalities. Also, rapid improvement in ANC and platelet count could decrease the other induction complications of infection & bleeding, further improving survival.

A Meta-Analysis on the Use of Intravenous Gamma Globulin and Corticosteroids in Children with Acute Immune Thrombocytopenic Purpura.

To determine the difference in proportion of patients who achieved a rise in platelet count and to determine the risk difference of adverse events in patients with acute immune thrombocytopenic purpura treated with corticosteroids or gamma globulin (IVIG). Medline, EMBASE, Pediatric Hematology and Oncology, Pediatrics and Journal of Pediatrics (all up to 2005) and personal collections of the authors. Systematic search of articles utilizing a search strategy was performed to identify relevant articles according to prior inclusion and exclusion criteria. Fixed effects and random effects models were used to determine summary effect estimates. Difference in proportion of patients who achieved the desired platelet count and risk difference of adverse events between treatment groups. Analysis of 9 randomized controlled trials showed that IVIG produced an additional 12–14% increase in proportion of patients with platelet count >20 x 109/L and 15% increase in proportion of patients with platelet count >50 x 109/L on days 2 to 4. No significant differences were seen between the treatment groups on days 14 and 28 except for platelet count >50 x 109/L. More patients in oral steroid treated group had adverse events compared to IVIG treated group but no differences were noted in the parenteral treated group. IVIG is more effective compared to corticosteroids in raising the platelet count during the early part of treatment. IVIG and parenteral steroids shows less adverse events as compared to oral steroid.

Apoptosis in the OC-k3 immortalized cell line treated with different agents.

The aim of this study is to outline the mechanisms leading cochlear cells to die. We utilized an immortalized cell line (OC-k3 cells) derived from the organ of Corti of transgenic mice in order to perform in-depth biochemical studies with no limitations on sample size and number. We probed these cells with cisplatin and gentamicin, two drugs which display in vivo undesired ototoxic side-effects. We investigated cell viability, reactive oxygen species (ROS) production and glutathione (GSH) levels and tested the effects of different concentrations of cisplatin and gentamicin from 0 to 48 h. Results show that cells undergo a dose- and treatment-time-dependent apoptosis characterized by nuclear fragmentation, integrity of the cell membrane and mitochondria, and absence of DNA endonuclease activity. During the early part of treatment, ROS production increases and intracellular GSH decreases, probably due to the activation of protein kinase C alpha. Use of antioxidants such as N-acetylcysteine, GSH and vitamin C rescues cells from apoptosis almost completely. Overall, these data indicate that ROS generation might play a central role in inducing inner ear cell apoptosis and may have an additive role in the ageing process.

Cell kinetics and repopulation mechanisms during multifraction irradiation of spheroids

Background and purpose: The objective of the present study was to evaluate the predictive potential of cell kinetic parameters and repopulation rates determined by flow cytometry during multifraction irradiation of spheroids, a system in which the fate of all cells can be determined with high precision. Ultimately, similar analytical techniques should provide a reproducible and prognostically significant clinical predictive assay. Materials and methods: Multicellular spheroids of Chinese hamster V79 lung cells were irradiated with 2.5 Gy of 250 kVp X-rays twice daily to a total dose of 25 Gy. Repopulation parameters and cell kinetic parameters were followed throughout the irradiation period and for 5 days after completion of exposure. Results: (1) Regrowth (RG) took place early during multifraction irradiation. (2) Potential doubling time ( T pot) decreased steadily from the early part of treatment, remaining of short duration until the spheroids almost attained the pre-treatment number of clonogenic cells. (3) Accelerated repopulation was mainly due to a decreased cell loss factor ( Φ) and increased growth fraction (GF), although a modest decrease in cell cycle time ( t c) was suggested. (4) Φ decreased during exponential RG. (5) Other parameters such as observed doubling time ( t d) and labelling index (LI) paralleled these findings. Conclusions: Clonogen repopulation that began early in the irradiation scheme and accelerated rapidly is not consistent with the prevailing view that accelerated repopulation begins several weeks into clinical protocols. Also, pre-treatment T pot did not adequately estimate the repopulation speed in the spheroids. Equivalent studies in animal tumour systems, and then in the clinic, are consequently indicated and of some urgency.

Tumour pH and response to chemotherapy: an in vivo 31P magnetic resonance spectroscopy study in non-Hodgkin's lymphoma

Serial image-localized 31P magnetic resonance spectroscopy studies were performed in nine patients with newly diagnosed non-Hodgkin's lymphoma (NHL) during the early part of treatment with chemotherapy. The pre-treatment intracellular pH (pHi) of the tumours ranged from 6.97 to 7.61 for high-grade NHL (n = 3), and 7.16 to 7.39 for low-grade NHL (n = 5). A pH of 7.24 was recorded in a patient with intermediate-grade NHL. Slice-to-slice variation in tumour pHi in spectra obtained with a one-dimensional chemical shift imaging (1D-CSI) technique varied from zero to 0.5 pH units. The largest variation was seen in high-grade tumours. Slice-to-slice variation may reflect tumour heterogeneity. Alkaline shifts in tumour pHi of 0.14 to 0.45 pH units were seen in six patients following chemotherapy. Maximal change in tumour pH was related temporally to increases in the phosphodiester/beta-adenosine triphosphate ratio, and occurred before alterations in tumour size were documented. Cell death and necrosis may be associated with an alkaline shift in pHi due to cessation of H(+)-producing processes and release of basic components of proteins. An alkaline shift in tumour pHi may therefore be an early metabolic marker of response to chemotherapy.

Relationships between clinical effects and monoamine metabolites and amino acids in sulpiride-treated schizophrenic patients

Twenty-four acutely ill schizophrenic patients (DSM-III-R), 18-42 years old, were treated for 6 weeks with sulpiride. Sulpiride was administered in three different daily dosages (400, 800 or 1200 mg) according to a double dummy blind randomized administration schedule. The psychopathology of the patients was rated by the Comprehensive Psychopathological Rating Scale (CPRS) and the Nurse's Observation Scale for Inpatient Evaluation (NOSIE). The monoamine metabolites homovanillic acid (HVA), 5-hydroxy-indoleacetic acid (5-HIAA), 4-hydroxy-3-methoxy-phenylglycol (HMPG) and the amino acids tyrosine, tryptophan, glutamate and glutamine were measured in serum before and once a week during sulpiride treatment. There were no significant correlations between the CPRS or the NOSIE morbidity scores and the biochemical measures before drug treatment. HVA levels were not correlated to rating scores during treatment, but after 6 weeks HVA had decreased significantly in the patients with a good response but not in the patients with a poor response. A negative relationship between 5-HIAA levels and depressive and negative symptoms was found. Non-responders according to the subscale for depression had low 5-HIAA levels throughout the treatment. An increase of tryptophan was correlated to improvement in the early part of treatment. High levels of glutamate or glutamine were found in non-responders before treatment. During treatment an increase of the glutamate level was correlated to improvement. Low levels of glutamine were related to improvement according to global and NOSIE (total) rating scores. Peripheral biochemical measures may be a valuable tool in the study of pathophysiological mechanisms and treatment effects in patients with schizophrenia.

Cranial electrostimulation (CES) use in the detoxification of opiate-dependent patients

This paper reviews the scientific literature on cranial electrostimulation (CES) as a non-chemical means to alleviate opiate withdrawal symptoms. CES involves applying small amounts of electrical stimulation through electrodes applied to the skin surface over the cranium. The paper summarizes major theories (gate, endorphin, and Chinese acupuncture) which attempt to explain how CES may help alleviate drug withdrawal and craving. Two of the studies reviewed show that CES patients experienced more severe withdrawal during the early part of treatment than comparison groups of methadone patients. Other studies show that CES patients did better than methadone patients. The findings from all studies reviewed, however, were limited because of low participation rates, high dropout rates, difficulties in blinding subjects and evaluators, and the absence of standardized procedures and equipment. The evidence reviewed suggests that CES is a promising line of inquiry for continued efforts to develop nonchemical ways to detoxify opiate-dependent individuals. Improved research designs, larger sample sizes, more integrity in data collection, and improved data analysis are needed in the future.

Pharmacologic Therapy for the Hyperlipidemic Patient

Drug therapy should be instituted only after appropriate diet treatment has been started and adequate baseline lipid and lipoprotein values are established. Nicotinic acid is useful in treating most lipoprotein disorders and the cutaneous flushing that develops during the early part of treatment is usually alleviated by aspirin. Cholestyramine and colestipol are nonabsorbable resins whose use is limited to type II hyperlipoproteinemia. Clofibrate is primarily effective in lowering triglyceride levels, but its clinical use has considerably declined following the World Health Organization study results that reported increased morbidity and mortality rates among patients receiving this drug. Based on the finding of increased mortality among a subset of patients participating in the Coronary Drug Project, dextrothyroxine is only recommended for treating patients who do not have clinically evident atherosclerotic heart disease. Probucol lowers total and low-density lipoprotein cholesterol levels, but has the undesirable effect of simultaneously reducing high-density lipoprotein levels.