Biomedical subjects

M Koshy

Publications and source records attributed to M Koshy.

At least 19 recordsLinked to original sources

PubMed2001

Stem cell transplantation eliminates alloantibody in a highly sensitized patient.

Highly sensitized patients are forced to stay on transplant waiting lists for many years and ultimately may never find a donor. Peripheral blood stem cell (PBSC) transplantation may provide a strategy to decrease host alloreactivity through the production of a chimeric state. We investigated alloreactivity and chimerism in a highly sensitized 40-year-old patient with sickle cell disease who underwent a nonradiation based conditioning regimen consisting of fludarabine, ATG, and high dose melphalan, for allogeneic stem cell transplant. Host monocytes and lymphocytes became donor in origin by day 14. PRA, initially 100% pretransplant, fell to 0 by day 263. Anti-red blood cells antibody became undetectable by day 152. The use of a new nonradiation-based conditioning regimen enabled successful engraftment of allogeneic donor PBSCs and the elimination of alloantibody. As new less toxic conditioning regimens are developed, PBSC transplantation might provide a new solution to allosensitization.

Adult↗

PubMed2001

Purified poloxamer 188 for treatment of acute vaso-occlusive crisis of sickle cell disease: A randomized controlled trial.

CONTEXT: Sickle cell disease (SCD) can cause severe painful episodes that are often thought to be caused by vaso-occlusion. The current therapy for these uncomplicated painful episodes includes hydration, oxygen, and analgesics. Purified poloxamer 188 may increase tissue oxygenation and thereby reduce inflammation, pain, and the overall duration of such painful episodes in patients with SCD. OBJECTIVE: To compare the duration of painful episodes in patients with SCD treated with purified poloxamer 188 to that of similar episodes experienced by patients who receive a placebo. DESIGN AND SETTING: Randomized, double-blind, placebo-controlled, intention-to-treat trial conducted between March 1998 and October 1999 in 40 medical centers in the United States. PARTICIPANTS: Two hundred fifty-five patients with SCD (aged 9-53 years) who had a painful episode sufficiently severe to require hospitalization and narcotic analgesics. INTERVENTION: Patients were randomly assigned to receive an intravenous infusion of purified poloxamer 188, 100 mg/kg for 1 hour followed by 30 mg/kg per hour for 47 hours (n = 127), or a matching volume of saline placebo (n = 128). MAIN OUTCOME MEASURE: Duration of the painful episode, from randomization to crisis resolution. RESULTS: Mean (SD) duration of the painful episodes was 141 (42) hours in the placebo group compared with 133 (41) hours in those treated with purified poloxamer 188, a 9-hour reduction (P =.04). Subset analyses indicated an even more pronounced purified poloxamer 188 effect in children aged 15 years or younger (21 hours; P =.01) and in patients who were receiving hydroxyurea (16 hours; P =.02). Finally, the proportion of patients achieving crisis resolution was increased by purified poloxamer 188 (65/126 [52%] vs 45/123 [37%]; P =.02). Similar results were observed in children aged 15 years or younger (22/37 [60%] vs 10/36 [28%]; P =.009) and in patients who were also receiving hydroxyurea (12/26 [46%] vs 4/28 [14%]; P =.02). CONCLUSIONS: A decrease in the duration of painful episodes and an increase in the proportion of patients who achieved resolution of the symptoms were observed when the purified poloxamer 188-treated patients were compared with the patients receiving placebo. However, the difference between these groups was significant but relatively small. In subgroup analysis, a more significant effect on both parameters was observed in children and in patients who were receiving concomitant hydroxyurea. It is important to confirm both of these observations in further prospective trials.

Adolescent↗

PubMed2001

Short-term sequelae of minor head injury (6 years experience of minor head injury clinic).

PURPOSE: It is known that post-concussive symptoms may persist after mild head injury. However, the majority of those patients are denied follow-up or support. A minor head injury clinic was thus established in North Staffordshire Hospital in 1993 to address these problems. METHODS: Patients 16-65 years old attending hospital with minor head injury were invited to attend the clinic two weeks after presentation. A specialized brain injury nurse and/or assistant clinical psychologist assessed them. Patients with persistent symptoms were invited to a second assessment four weeks later. RESULTS: One thousand two hundred and fifty-five patients were invited for first assessment, the most common cause of head injury was assault (454) followed by road traffic accident (334). Six hundred and sixteen patients did not attend the first assessment; most of non-attendees were those who had been assaulted (281). Six hundred and thirty-nine patients attended, (472) were male, their mean age was 33. Forty-three per cent of them had history of recent alcohol intake. One third had had a previous head injury. Although 391 attendees were in regular employment, 219 patients were unable to return to work 2 weeks after discharge (56%), and 49 people were still off sick 6 weeks after the injury. The most common complaints at both assessments were fatigue, headache, dizziness, irritability, sleep disturbances, poor concentration and poor memory in that order. CONCLUSION: This study shows a significant number of patients with minor head injury still complaining of post concussive symptoms, which may contribute to a delay in return to work. The high incidence of non-attendance among the assaulted victims may indicate that this group needs to be more effectively targeted. Further study to look at the longer-term consequences of minor head injury is required in view of these findings.

Adolescent↗

PubMed2001

Allogeneic stem cell transplantation for sickle cell disease. A study of patients' decisions.

Allogeneic stem cell transplantation is increasingly considered as a curative though risky treatment option for adults with sickle cell disease. Little is known about attitudes of adult patients and their health care providers regarding the risks and benefits of transplantation. A survey of 100 patients and their health care providers was undertaken. Assessment of risk was by a reference gamble paradigm. Comparison was made of the characteristics of those accepting substantial risk vs those not accepting risk, as well as assessment of agreement on risks recommended by health care providers and accepted by patients. Sixty-three of 100 patients were willing to accept some short-term risk of mortality in exchange for the certainty of cure. Fifteen patients were willing to accept more than 35% mortality risk. No differences in patient or disease-related variables were identified between those accepting risk and those not accepting risk. There was no agreement between the recommendations of health care providers and the risk accepted by patients. A substantial proportion of adults with sickle cell disease are interested in curative treatment, at the expense of considerable risk. The decision to accept risk is influenced by individual patient values that cannot be easily quantified and that do not correlate with the assessment of the health care provider. Given the substantial interest in curative therapy, education about and consultation for allogeneic stem cell transplantation in sickle cell patients should be encouraged.

Adult↗

PubMed2000

2-deoxy 5-azacytidine and fetal hemoglobin induction in sickle cell anemia.

Augmentation of the fetal hemoglobin (HbF) levels is of therapeutic benefit in patients with sickle cell anemia. Hydroxyurea (HU), by increasing HbF, lowers rates of pain crisis, episodes of acute chest syndrome, and requirements for blood transfusions. For patients with no HbF elevation after HU treatment, augmentation of HbF levels by 5-aza-2'-deoxycytidine (5-aza-CdR, decitabine) could serve as an alternate mode of treatment. Eight adult patients participated in a dose-escalating phase I/II study with 5-aza-CdR at doses ranging from 0.15 to 0.30 mg/kg given 5 days a week for 2 weeks. HbF, F cell, F/F cell, gamma-globin synthesis ratio, complete blood count, and chemistry were measured. The average gamma-globin synthesis relative to non-alpha-globin synthesis prior to therapy was 3.19% +/- 1.43% and increased to 13.66% +/- 4.35% after treatment. HbF increased from 3.55% +/- 2.47% to 13.45% +/- 3.69%. F cells increased from 21% +/- 14.8% to 55% +/- 13.5% and HbF/F cell increased from 17% to 24%. In the HU nonresponders HbF levels increased from 2.28% +/- 1.61% to 2.6% +/- 2.15% on HU, whereas on 5-aza-CdR HbF increased to 12.70% +/- 1.81%. Total hemoglobin increased by 1 g/dL in 6 of 8 patients with only minor reversible toxicities, and all patients tolerated the drug. Maximum HbF was attained within 4 weeks of treatment and persisted for 2 weeks before falling below 90% of the maximum. Therefore 5-aza-CdR could be effective in increasing HbF in patients with sickle cell anemia who failed to increase HbF with HU. Demonstration of sustained F levels with additional treatment cycles without toxicity is currently being performed.

Adolescent↗

PubMed2000

Fludarabine-based conditioning for allogeneic transplantation in adults with sickle cell disease.

Although allogeneic transplantation can be curative for patients with sickle cell disease, the toxicity of conditioning regimens has precluded its use in adults with significant end-organ damage. Newer conditioning regimens have been developed that are less toxic and that may broaden the applicability of allogeneic transplantation in this disorder. We report two adults with end-stage sickle cell disease, who underwent allogeneic transplantation from an HLA-identical sibling donor after conditioning with fludarabine/melphalan and ATG. Both patients had been extensively transfused and one had multiple RBC antibodies. One of the patients also had end-stage renal disease, and was dialysis dependent. Engraftment occurred promptly in both patients. Both achieved 100% donor chimerism and both were free of pain crises after transplant. The first patient died of a respiratory failure related to chronic graft-versus-host disease (GVHD) on day 335 after transplantation. The second patient developed severe gastro-intestinal GVHD and TTP and died on day 147 after transplantation. Conditioning with fludarabine/melphalan and ATG followed by allogeneic stem cell transplantation resulted in prompt and reliable engraftment in adults with end-stage sickle cell disease. The incidence of severe GVHD was unacceptably high and may be related to the ethnicity of the patients or to the inflammatory state associated with pre-existing sickle cell disease.

Adult↗

PubMed2000

Study of biodistribution of methotrexate-loaded bovine serum albumin nanospheres in mice.

Nanospheres made from natural hydrophilic polymers have been proved efficient in terms of better drug-loading capacity, biocompatibility, and possibility less opsonization by reticuloendothelial system (RES) through an aqueous stearic barrier. Hence, nanospheres containing methotrexate were prepared from bovine serum albumin (BSA) by a novel pH coacervation method. A drug-to-polymer ratio study was carried out to determine the carrier capacity. The batch with the highest drug loading was subjected to in vitro analysis. It was found to provide a slow release after an initial burst release. Biodistribution of nanosphere-bound drug was compared with that of free drug in mice. It was observed that the percentage increase in drug distribution to the lungs, liver, and spleen was markedly high from the nanosphere when compared to free drug.

Animals↗

PubMed1999

The perioperative complication rate of orthopedic surgery in sickle cell disease: report of the National Sickle Cell Surgery Study Group.

Orthopedic disease affects the majority of sickle cell anemia patients of which aseptic necrosis of the hip is the most common, occurring in up to 50% of patients. We conducted a multicentered study to determine the perioperative complications among sickle cell patients assigned to different transfusion regimens prior to orthopedic procedures: 118 patients underwent 138 surgeries. The overall serious complication rate was 67%. The most common of these were excessive intraoperative blood loss, defined as in excess of 10% of blood volume. The next most common complication was sickle cell-related events (acute chest syndrome or vaso-occlusive crisis), which occurred in 17% of cases. While preoperative transfusion group assignment did not predict overall complication rates, higher risk procedures were associated with significantly higher rates of overall complications. Transfusion complications were experienced by 12% of the patients. Two patients died following surgery. Both deaths were associated with an acute pulmonary event. The 52 patients undergoing hip replacements experienced the highest rate of complications with excessive intraoperative blood loss occurring in the majority of patients. Sickle cell-related events occurred in 19% of patients, and surgical complications occurred after 15% of hip replacements and included postoperative hemorrhage, dislocated prosthesis, wound abscess, and rupture of the femoral prosthesis. There were twenty-two hip coring procedures. Acute chest syndrome occurred in 14% of the patients. Overall, decompression coring was a safer, shorter operation. A randomized prospective trial to determine the perioperative and long-term efficacy of core decompression for avascular necrosis of the hip in sickle cell disease is needed. In conclusion, this study demonstrates a high rate of perioperative complications despite compliance with sickle cell perioperative care guidelines. Pulmonary complications and transfusion reactions were common. This study supports the results previously published by the National Preoperative Transfusion in Sickle Cell Disease Group. These results stated that a conservative preoperative transfusion regimen to bring hemoglobin concentration to between 9 and 11 g/dl was as effective as an aggressive transfusion regimen in which the hemoglobin S level was lowered to 30%.

Adolescent↗

PubMed1999

Elevated levels and functional capacity of soluble CD40 ligand in systemic lupus erythematosus sera.

OBJECTIVE: To measure soluble CD40 ligand (sCD40L) in sera from patients with systemic lupus erythematosus (SLE) and to study the functional capacity of sCD40L in mediating B cell activation. METHODS: A 2-site enzyme-linked immunosorbent assay (ELISA) was used to measure sCD40L in the sera of 66 SLE patients, 30 disease control patients, and 23 healthy subjects. Induction of B cell activation antigen expression was used to assess the functional capacity of sCD40L in SLE sera. RESULTS: The mean concentration of sCD40L was statistically significantly higher (P < 0.0001) in SLE patients than in disease controls or healthy subjects, and segregation of SLE patients by severe, moderate, or mild extent of disease showed a relationship between disease severity and sCD40L concentration. Western blot analysis demonstrated the presence of the 18-kd band of sCD40L in SLE sera, and the results of a 1-site ELISA protocol suggested that some of the product in SLE sera was present in dimer or trimer form. Functional studies showed that 10 ng/ml of recombinant CD40L, a level present in some SLE sera, induced increased expression of CD95 on B cells. Several SLE sera also induced CD95 or CD86 on Ramos B cells, a result that was inhibited by anti-CD40L monoclonal antibodies. CONCLUSION: The soluble form of CD40L is present in the sera of most patients with SLE and may have the capacity to mediate B cell activation. Aberrant expression of CD40L might be predicted to result in activation of bystander B cells, including those that have encountered self antigens, and to contribute to autoantibody secretion.

Antigens, Surface↗

PubMed1999

Immune-deficient bronchiectasis associated with X-linked lymphoproliferative disease.

Bronchiectasis may occur with various congenital and acquired immunodeficiency diseases. The association of bronchiectasis and the X-linked lymphoproliferative disease (XLP), also known as Duncan's disease is unknown. We describe the case of a 39-year-old man with XLP, the oldest surviving, who developed chronic bronchiectasis with hemoptysis and required a pneumonectomy to control his symptoms.

Adult↗

PubMed1998

Chronic lymphocytic leukemia B cells can express CD40 ligand and demonstrate T-cell type costimulatory capacity.

Chronic lymphocytic leukemia (CLL) is characterized by a clonal expansion of CD5(+) B cells in the peripheral blood. Associated immune aberrations include abnormal Th-cell function and pathogenic autoantibodies. Under most circumstances, CLL B cells do not proliferate in culture and express a limited repertoire of surface antigens, including CD19, CD20, CD23, CD27, CD40, and CD70. In this report, we demonstrate that freshly isolated B cells from a subset of CLL cases constitutively express CD40 ligand (CD40L, CD154), a member of the tumor necrosis factor family which is normally expressed by activated CD4(+) T cells and mediates T-cell-dependent B-cell proliferation and antibody production. The degree of CD40L expression varied considerably among the CLL cases examined. CD40L was detected in purified CLL B cells by immunofluorescence flow cytometry, by RT-PCR, and by immunoprecipitation. To demonstrate that CD40L in the CLL B cells is functional, we used irradiated CLL cells to stimulate IgG production by target, nonmalignant B cells in coculture. The CLL B cells induced IgG production by normal B cells to a similar degree as did purified T cells in a process which was partially inhibited by monoclonal antibody to CD40L. This is one of the first reports of CD40L expression in a B-cell tumor. The data suggest that CD40L in the tumor cells may be a factor in the generation of pathologic antibodies by normal B cells in some patients with CLL.

B-Lymphocytes↗

PubMed1998

Surgery in patients with hemoglobin SC disease. Preoperative Transfusion in Sickle Cell Disease Study Group.

While surgery is commonly required for complications related to hemoglobin SC (HbSC) disease, little is known about the perioperative complications or the indications for preoperative transfusion in this group. We describe the patient characteristics, preoperative transfusion regimens, and outcome in 92 patients with HbSC and sickle-variants undergoing elective surgery. Thirty-eight percent of the patients were transfused preoperatively. Patients transfused were more likely to have been hospitalized in the year prior to the surgery and scheduled for abdominal procedures. Abdominal and ear, nose and throat procedures were the most common surgeries in our study. The overall complication rate was 18% and sickle cell-related complications occurred in 9% of patients. In patients undergoing intra-abdominal procedures, the incidence of sickle cell-related complications was significantly higher in those patients not transfused prior to their surgery (35 vs. 0%). There were two deaths. We recommend selective use of preoperative transfusion in patients with HbSC disease undergoing surgery. Transfusion appears to be beneficial in abdominal cases but is not necessary with minor procedures such as myringtomy.

Adult↗

PubMed1998

Is the incidence of appendicitis reduced in patients with sickle cell disease?

BACKGROUND: Patients with sickle cell disease (SCD) often present with abdominal pain, usually attributable to vasoocclusion. Experience at a single institution suggested that appendicitis was a rare cause of abdominal symptoms in this population. OBJECTIVE: We sought to determine whether the incidence of appendicitis was significantly lower in patients with SCD than in the population at large. METHODS: A 17-year retrospective chart review was performed at Rainbow Babies and Children's Hospital, Cleveland, OH, to determine the approximate incidence of acute appendicitis (AA) in patients with SCD. In addition, we performed a statistical analysis comparing the incidence of AA among SCD patients enrolled in the Cooperative Study of Sickle Cell Disease with that in the general population. RESULTS: Only two patients with SCD with pathologically confirmed AA were identified among approximately 200 patients followed at our institution during a 17-year period ( approximately 3500 patient-years), yielding an incidence rate of 5.7 cases per 10 000 patient-years. Among 3765 patients with SCD enrolled in the Cooperative Study of Sickle Cell Disease followed for a mean of 5.3 years (19 886 patient-years), a maximum of 9 cases of AA were identified, yielding an incidence rate of 4.5 cases per 10 000 patient-years. Based on data from the National Hospital Discharge Survey of 1978 to 1981, the incidence rate of AA in the general population (0 to 44 years of age) is approximately 16 per 10 000 patient-years. Paired t test analysis demonstrated a highly significant difference (P < .001) when comparing the incidence of AA among patients enrolled in the Cooperative Study of Sickle Cell Disease and the population at large. CONCLUSION: AA is an unusual event in patients with SCD. The likelihood of developing appendicitis in SCD patients is less than one third of that for the population at large. Conservative therapy is warranted in the large majority of patients with SCD who present with acute abdominal pain. Surgical exploration is best limited to patients with clear evidence of potential surgical pathology or progressive findings during a period of observation. The biologic basis of our findings remains unknown.

Acute Disease↗

PubMed1997

RheothRx (poloxamer 188) injection for the acute painful episode of sickle cell disease: a pilot study.

RheothRx (Glaxo Wellcome Inc, Research Triangle Park, NC; poloxamer 188) Injection is a nonionic surfactant with hemorrheologic properties that suggest it may be useful in treating acute painful episodes (vasoocclusive crises) of sickle cell disease (SCD). We conducted a randomized, double-blind, placebo-controlled pilot study to evaluate the safety and efficacy of poloxamer, formulated as RheothRx Injection, in 50 patients with SCD. Patients with moderate to severe painful episodes requiring parenteral analgesics were randomized to receive a 48-hour infusion of either RheothRx or placebo. Pain was assessed every 4 hours. Efficacy endpoints included: (1) painful episode duration, (2) days of hospitalization, (3) quantity of analgesics used, and (4) pain intensity scores. Three subgroups of patients were considered for efficacy analyses based on the actual duration of the study drug infusion and the completeness of pain score data collection. Compared with placebo and depending on the subgroup, RheothRx-treated patients showed a 16% to 45% decrease in duration of painful episodes, a 1- to 2-day reduction in hospital stay, a threefold to fivefold reduction in analgesic requirements, and a 1-point reduction (using a 5-point scale) in average pain intensity scores at 72 hours. RheothRx was well tolerated; no clinically significant differences were observed between treatments with respect to adverse experiences or other safety measures. In addition, there were no differences between treatment groups in the incidence of recurrent painful episodes. In this study, RheothRx significantly reduced total analgesic use and pain intensity and showed trends to shorter duration of painful episodes and total days of hospitalization. In patients with moderate to severe vasoocclusive pain, RheothRx was safe and may offer a therapeutic benefit.

Adolescent↗

PubMed1997

Cholecystectomy in sickle cell anemia patients: perioperative outcome of 364 cases from the National Preoperative Transfusion Study. Preoperative Transfusion in Sickle Cell Disease Study Group.

Cholecystectomy is the most common surgical procedure performed in sickle cell anemia (SCA) patients. We investigated the effects of transfusion and surgical method on perioperative outcome. A total of 364 patients underwent cholecystectomy: group 1 (randomized to aggressive transfusion) 110 patients; group 2 (randomized to conservative transfusion) 120 patients; group 3 (nonrandomized nontransfusion) 37 patients; and group 4 (nonrandomized transfusion) 97 patients. Patients were similar except group 3 patients were more likely to be female, over 20 years old, smokers, and more healthy by American Society of Anesthesiologists (ASA) physical status score. Total complication rate was 39%: sickle cell events 19%; intraoperative or recovery room events 11%; transfusion complications 10%; postoperative surgical events 4%; and death 1%. Group 3 patients had the highest incidence of sickle cell events (32%). Open cholecystectomies were performed in 58% and laparoscopic in 42%. Laparoscopic patients were younger and more healthy by ASA score. Laparoscopic patients had longer anesthesia time (3.2 v 2.9 hours), but shorter hospitalization time (6.4 days v 9.8). Complications were similar between these two groups. We conclude that SCA patients undergoing cholecystectomy have a high perioperative morbidity, and the incidence of sickle cell events may be higher in patients not preoperatively transfused. We recommend a conservative preoperative transfusion regimen, and we encourage the use of the laparoscopic technique for SCA patients undergoing elective cholecystectomy.

Adolescent↗

PubMed1996

Increased expression of CD40 ligand on systemic lupus erythematosus lymphocytes.

The specificity of T cell help for B cell activation and differentiation is maintained by the brief expression on the T cell surface, following T cell receptor-mediated triggering, of CD40 ligand (CD40L). Interaction of T helper (Th) cell CD40L with B cell CD40 induces B cell activation, cell surface expression of activation antigens, proliferation, and initiation of immunoglobulin isotype switch. We predicted that in patients with systemic lupus erythematosus (SLE), in whom Th cell-dependent production of autoantibodies results in immune complex-mediated tissue damage, CD40L expression might be augmented, prolonged, or abnormally regulated. Baseline expression of CD40L was increased in some SLE patients studied, when compared with control subjects. While Th cells from normal subjects (n = 14) and rheumatic disease control patients (n = 9) showed maximal expression of CD40L, after in vitro activation with phorbol myristate acetate (PMA) and ionomycin, at 6 h of culture with diminished levels observed at 24 and 48 h, Th cells from SLE patients (n = 19) maintained high level cell surface expression of CD40L through 24 and 48 h of culture. The prolonged expression of CD40L was functionally significant, as 24 h-activated SLE T cells, when cocultured with target B cells, induced greater B cell surface CD80 (B7-1) expression than did 24 h-activated normal T cells. These results document impaired regulation of CD40L expression in SLE T cells and identify an important potential target for therapy in this systemic autoimmune disease.

Adult↗

PubMed1996

Pregnancy in sickle cell disease: experience of the Cooperative Study of Sickle Cell Disease.

OBJECTIVE: To determine the maternal and fetal outcomes of pregnancy in women with sickle cell disease. METHODS: The subjects were part of a cohort recruited from 19 centers for a prospective study of the clinical course of sickle cell disease. Each participant was evaluated using a structured protocol in which steady-state data and information on both sickle- and non-sickle-related events were collected. The rates of antepartum and intrapartum complications were tallied for pregnancies carried to delivery. Fetal outcome was assessed according to gestational age, birth weight, and Apgar score. Differences among genotypes in event rates were assessed using Fisher exact test. Differences in gestational age and birth weight, and predictors of these outcomes, were assessed using analyses of covariance. RESULTS: Two hundred eighty-six of the 445 reported pregnancies proceeded to delivery. Non-sickle-related antepartum and intrapartum complication rates were comparable with those of African-American women who did not have sickle cell disease. One of the two deaths observed during this study was directly related to the presence of sickle cell disease. Rates of maternal morbidity from sickle cell disease were the same during pregnancy as during the nonpregnant state. Ninety-nine percent of those pregnancies carried to delivery resulted in a live birth. Twenty-one percent of the infants born to women of the SS genotype were small for gestational age (SGA). Preeclampsia and acute anemic events were identified as risk factors for SGA infants. CONCLUSIONS: Those caring for women with sickle cell disease should support them if they desire to have children.

Adult↗

PubMed1996

Continuing care for adult patients with sickle cell disease.

Continuing services for patients with sickle cell disease focuses on holistic care. Participation in preventive medicine principles of health management, avoidance of risk behaviors and seeking appropriate counseling for education, employment, healthy lifestyles, and productive living are beneficial to the patient.

Adult↗