Effect of storage time of platelet products on clinical outcomes after transfusion: a systematic review and meta-analyses.

BACKGROUND: Prolonged storage improves availability of platelet products but could also influence safety and efficacy. This systematic review and meta-analyses summarize and quantify the evidence of the effect of storage time of transfused platelets on clinical outcomes. METHODS: A systematic search in seven databases was performed up to February 2016. All studies reporting storage time of platelet products and clinical outcomes were included. To quantify heterogeneity, I² was calculated, and to assess publication bias, funnel plots were constructed. RESULTS: Twenty-three studies reported safety outcomes and fifteen efficacy outcomes. The relative risk of a transfusion reaction after old platelets compared to fresh platelets was 1·53 (95% confidence interval (CI): 1·04-2·25) (12 studies). This was 2·05 (CI:1·47-2·85) before and 1·05 (CI: 0·60-1·84) after implementation of universal leucoreduction. The relative risk of bleeding was 1·13 (CI: 0·97-1·32) for old platelets compared to fresh (five studies). The transfusion interval was 0·25 days (CI: 0·13; 0·38) shorter after transfusion of old platelets (four studies). Three studies reported use of platelet products: two for haematological patients and one for trauma patients. Selecting only studies in haematological patients, the difference was 4·51 units (CI: 1·92; 7·11). CONCLUSION: Old platelets increase the risk of transfusion reactions in the setting of non-leucoreduction, shorten platelet transfusion intervals, thereby increase the numbers of platelet transfusions in haematological patients, and may increase the risk of bleeding.

Effect of platelet storage time on platelet measurements: a systematic review and meta-analyses.

BACKGROUND: The storage time of platelet products negatively affects bacterial safety and platelet function. However, low maximum storage time increases outdating of valuable products. Thus, to quantify the effect of platelet storage time on platelet measurements after platelet transfusion, a systematic review and meta-analyses were performed. METHODS: Reports and meeting abstracts of randomized trials and observational studies, performed in humans, reporting platelet measurements after transfusion of platelet products of different storage times, were selected until February 2016. Meta-analyses were performed for four different storage time contrasts, each answering a different question. Random-effects models were used to account for substantial heterogeneity and the weighted mean differences calculated. RESULTS: Our search strategy yielded 4234 studies of which 46 papers satisfied the inclusion criteria. As judged by the 1-h corrected count increment, transfusions of fresher platelets compared to stored platelets showed better increment. The weighed mean difference varied from 2·11 (95%CI: 1·51-2·71) to 2·68 (95%CI: 1·92-3·45). For the 24-h corrected count increment, the weighted mean difference varied from 1·36 (95%CI: 0·12-2·60) to 1·68 (95%CI: 1·07-2·28) depending on the contrast. Recovery and survival of old platelets as percentage of fresh platelets were 81% and 73% for the original definition contrast. For the extended storage contrast, recovery and survival were 75% and 68%. CONCLUSIONS: Fresh platelets were superior to old platelets for all platelet measurements and for all storage time contrasts meta-analysed.

Clinical practice of platelet transfusions in haemato-oncology.

Platelets are prophylactically transfused to patients receiving myeloablative chemotherapy. The trigger can be adapted if a patient has risk factors for bleeding. We performed an international survey to quantify differences in transfusion policies. While platelet counts are most important, bleeding, fever, use of anticoagulants and invasive procedures also determine transfusion strategies. The largest variation of triggers was observed for lumbar punctures and removal of central venous catheters.

Long-term outcome of the Cloward procedure for single-level cervical degenerative spondylosis. Clinical and radiological assessment after a 22-year mean follow-up.

PURPOSE: To evaluate the long-term outcomes of the classical Cloward procedure in single-level cervical spondylosis. METHODS: A retrospective study of 28 patients who were affected by cervical degenerative spondylosis at C4-C7 segments and treated by the Cloward technique at a single level from 1985-1995 was conducted. The average follow-up period was 22 years (range, 17-27 years). Preoperative clinical complaints were recorded and compared to the current clinical status. Preoperative, 3-6 months postoperative and a current radiographic study were analysed by evaluating the segmental and global sagittal alignment of the cervical spine as well as the occurrence of adjacent disc degeneration. RESULTS: The most frequently operated segment was C5-C6 (57.1 %), followed by C6-C7 (32.1 %) and C4-C5 (7.1 %). Pain relief and symptom recovery experienced 3-6 months following the surgery was maintained at the most recent follow-up in 85 % of patients. Adjacent disc degeneration was detected in a total of 17 cases (60.7 %). Overall, a group of 14 cases (50 %) had increased lordosis at C2-C7 at the most recent follow-up, with a mean gain of 1.5º Cobb. According to Odom's criteria, 17 patients (60.8 %) presented with excellent clinical outcome, 6 (21.4 %) presented with good outcome, 5 had a (17.8 %) fair outcome, and none had a poor outcome. CONCLUSIONS: The Cloward technique provided excellent long-term clinical outcome in the treatment of single-level cervical degenerative spondylosis. There were no major alterations of the cervical sagittal balance, and the development of adjacent segment disease (ASD) was not specifically associated with the previous surgery.

Lumbar puncture in pediatric oncology: conscious sedation vs. general anesthesia.

BACKGROUND: Lumbar punctures (LP) generally have been performed with conscious sedation (CS) but are increasingly performed using general anesthesia (GA) owing to the belief that this is less distressing. The aim of this study was to compare these two methods concerning distress, discomfort, pain, well-being and security after the LP, and problems with the LP. PROCEDURE: Twenty-five children with cancer participated in this prospective, randomized, crossover study. Children, parents, and nurses completed a visual analogue scale questionnaire to evaluate the efficacy of CS and GA. In addition, sedation and anesthesia protocols were reviewed. RESULTS: The two methods seemed to be equivalent concerning distress, discomfort, pain, well-being and security after the procedure, and procedure problems. Most children (80%), parents (66%), and nurses (58%) preferred LP in CS. However, the LP was not performed in CS in five cases because the child did not cooperate. Younger children less often preferred CS. CONCLUSIONS: Outcomes for CS and GA in LP were similar. Although there were failures with the CS model, most preferred it to GA. LP in CS also saved time and medical resources. An alternative approach would be to have a pediatric anesthesiologist available at the oncology ward for these elective LPs to provide the sedation or anesthesia required by each individual.

Pain variations during cancer treatment in children: a descriptive survey.

Structural interviews were conducted with 66 children and their families to investigate how the experience of pain varied during cancer treatment. At diagnosis, 49% experienced cancer-related pain. Intense pain was more common at the beginning of treatment when it was often believed that pain treatment could be better. Procedure- and treatment-related pain were the major problems initially. Procedural pain gradually decreased, but treatment-related pain was constant and dominating. For some procedures pain was rated highest initially, lower during the second period, and higher again during the final part of treatment. Pain intensity measurement was seldom performed, and parents increasingly considered themselves better judges of their child's pain than professionals. Increased knowledge about pain and pain treatment in children with cancer, where most pain is iatrogenic, will help us to meet the needs and demands of children and parents, and to reduce pain to a minimum.

Self-esteem, depression and anxiety among Swedish children and adolescents on and off cancer treatment.

Self-esteem, depression and anxiety were investigated in 51 Swedish children and adolescents, 8-18 y, on (n = 16) and off (n = 35) cancer treatment. The self-report measures "I Think I Am" (ITIA), the Children's Depression Inventory (CDI) and the Revised Children's Manifest Anxiety Scale (RCMAS) were used. Data were compared with data previously obtained by others for healthy Swedish children. Children and adolescents on treatment showed levels of self-esteem, depression and anxiety comparable to those of healthy children. However, children and adolescents off treatment reported higher depression and anxiety levels and lower psychological well-being and physical self-esteem than have been reported for healthy Swedish children. Seven children (14%) reported a high level of depression, six of whom were off treatment. The findings suggest that the period after treatment termination is characterized by a higher risk of psychosocial problems than is the actual treatment period.

Midazolam nasal spray reduces procedural anxiety in children.

OBJECTIVE: Anxiety and pain even in minor procedures are still great problems in pediatrics, not least in pediatric oncology. Conscious sedation is indicated when other means to overcome a child's fear fail. The aim of this study was to investigate whether intranasal administration of midazolam given before insertion of a needle in a subcutaneously implanted central venous port could reduce anxiety, discomfort, pain, and procedure problems. METHOD: Forty-three children with cancer participated in this randomized, double-blind, placebo-controlled, crossover study in which nasal administration of midazolam spray,.2 mg/kg body weight, was compared with placebo. Children, parents, and nurses completed a visual analog scale questionnaire to evaluate efficacy. RESULTS: Parents and nurses reported reduced anxiety, discomfort, and procedure problems for children in the midazolam group and would prefer the same medication at next procedure. They also reported pain reduction. Children reported reduced anxiety and procedure problems but reduction of pain and discomfort was not significant. No serious or unexpected side effects occurred. Nasal discomfort was the most common side effect (17/38 approximately 45%) and the primary reason for dropouts (8/43 approximately 19%). Anxiety varied with age but not with gender. When anxiety increased, the differences between midazolam and placebo increased. CONCLUSION: Nasal midazolam spray offers relief to children anxious about procedures, such as insertion of a needle in a subcutaneously implanted intravenous port, venous blood sampling, venous cannulation, etc. Its use, however, may be limited by nasal discomfort in some patients for whom rectal and oral routes might be alternatives.

Pain in paediatric oncology: interviews with children, adolescents and their parents.

Pain diagnostics and treatment are crucial components in the care of children with cancer. This study evaluated the extent and causes of pain, the use of methods for monitoring pain intensity, principles of pain management and adverse effects of pain treatment. In addition, care, support and information given to children and parents were evaluated. Structured interviews were conducted with 55 children with malignant disease and their parents. Pain was a common symptom and a major problem during different phases of cancer treatment and pain evaluation was unsystematic. Pain due to treatment and procedures was a greater problem than pain due to the malignant disease itself, and two thirds of the pain experienced by these children seemed to have iatrogenic origin. Younger children and children with short disease duration were more concerned about procedural pain. Parents and children thought that more efficient pain treatment was often possible. Parents claimed to judge their child's pain better than professionals, and children and parents wanted more information on different aspects of pain and pain treatment. Pain identification and treatment can be substantially improved through increased use of methods for pain evaluation and through giving enhanced information to families about pain and pain treatment.

Intensified treatment of acute childhood lymphoblastic leukaemia has improved prognosis, especially in non-high-risk patients: the Nordic experience of 2648 patients diagnosed between 1981 and 1996. Nordic Society of Paediatric Haematology and Oncology (NOPHO)

In a multinational, population-based study from the five Nordic countries (Denmark, Finland, Iceland, Norway and Sweden), 2648 children below 15 y of age were diagnosed with acute lymphoblastic leukaemia (ALL) in the years 1981-1996. The annual incidence was 3.9/100000 children and was stable throughout the study period. The development from regional or national protocols to common Nordic treatment protocols for all risk groups was completed in 1992 through a successive intensification of therapy, based on multidrug chemotherapy including pulses of methotrexate in high doses and avoidance of cranial irradiation in most children. For children with non-B-cell ALL (n=2602), the event-free survival (p-EFS) increased from 0.53+/-0.02 (diagnosed 7/81-6/86) to 0.67+/-0.02 (7/86-12/91) to 0.78+/-0.02 (1/92-12/96). The corresponding p-EFS values at 5 y were 0.57, 0.70 and 0.78, respectively. The main improvements were seen in the group of children with non-high risk leukaemia, with 5-y p-EFS values increasing from 0.60 to 0.76 and 0.85 for the three periods. In high-risk patients, progress has been moderate, especially in children with high white blood cell values at diagnosis. During the last 5-y period, only 10% of the patients received cranial irradiation in first remission while 90% of the patients received high doses of cytostatic infusions (methotrexate isolated or combined with cytarabinoside) and multiple intrathecal injections of methotrexate as CNS-adjusted treatment without any indication of an increased CNS relapse rate.

Diamond-Blackfan anaemia in a girl with a de novo balanced reciprocal X;19 translocation.

A 7 year old girl is described with congenital hypoplastic anaemia (Diamond-Blackfan anaemia, DBA) and an apparently balanced reciprocal translocation, 46,XX,t(X;19)(p21;q13). The girl has associated features including short stature, unilateral kidney hypoplasia, and a branchial cyst. Fluorescent in situ hybridisation (FISH) studies with 19q specific cosmids showed that the chromosome 19 breakpoint is located between the RYR1 and the XRCC11 loci spanning a physical region of 5 Mb. There is no family history of DBA and the parents and two healthy sibs have normal karyotypes. This is the first report of a balanced translocation associated with DBA and we suggest that the distinct phenotype has resulted from a de novo disruption of a functional gene. DBA can be inherited as an autosomal trait and our observation may indicate a candidate gene for the disorder in the 19q13 region.

Diamond-Blackfan anaemia: genetic homogeneity for a gene on chromosome 19q13 restricted to 1.8 Mb.

Diamond-Blackfan anaemia (DBA; MIM#205900) is a rare disorder manifested as a pure red-cell aplasia in the neonatal period or in infancy. The clinical hallmark of DBA is a selective decrease in erythroid precursors and anaemia. Other lineages are usually normal and the peripheral white blood cell count is normal. In approximately one-third of cases, the disease is associated with a wide variety of congenital anomalies and malformations. Most cases are sporadic, but 10-20% of them follow a recessive or a dominant inheritance pattern. A female with DBA and a chromosomal translocation involving chromosome 19q was recently identified. We undertook a linkage analysis with chromosome 19 markers in multiplex DBA families of Swedish, French, Dutch, Arabic and Italian origin. Significant linkage to chromosome 19q13 was established for dominant and recessive inherited DBA with a peak lod score at D19S197 (Zmax = 7.08, theta = 0.00). Within this region, a submicroscopic de novo deletion of 3.3 Mb was identified in a patient with DBA. The deletion coincides with the translocation break-point and, together with key recombinations, restricts the DBA gene to a 1.8-Mb region. The results suggest that, despite its clinical heterogeneity, DBA is genetically homogeneous for a gene in 19q13.

Parental reports of changes and challenges that result from parenting a child with cancer.

Cancer in a child leads to a more stressful family life, including problems in adjusting to the situation. The aim of this study was to identify the parents' experience of problems related to their child's/adolescent's cancer and the effect of those problems on the parents' life situation. Swedish parents of 15 children and adolescents with varying diagnoses and treatments were interviewed using qualitative methods. The interview data were analyzed by two researchers using a constant comparative method. The results included eight categories of problems influencing the parents' life situation: watching our child suffer; being governed by our child's disease; behaving differently as a family member; experiencing strong feelings and reactions; trying to cope; dealing with the reactions of others; finding support from others; and evaluating the quality of care. Seven of these categories validate previously reported parental concerns, but one, evaluating the quality of care, has not been previously reported. Study findings can be used to help sensitize health care personnel to the problems experienced by parents of children and adolescents with cancer and the capacity parents have to deal with the problems.

Development of a tool to measure the life situation of parents of children with cancer.

The aim of this study was to test the validity and reliability of the recently developed Life Situation Scale for Parents (LSS-P) among parents of children with cancer. One hundred and ten parents of seventy-four children and adolescents who visited three paediatric wards in Sweden filled out three instruments: The LSS-P, the Quality of Life Scale and the Family Support Scale. The reliability coefficient, Cronbach's alpha, was found to be 0.82 for the LSS-P. A factor analysis with orthogonal varimax rotation of 37 items of the LSS-P gave twelve factors. A higher order factor analysis reduced the factors to four (Care, Well-being, Social life and Preparedness), explaining the underlying dimensions to 57.9%. The total LSS-P correlated significantly with the Quality of Life Scale, and the higher order factor Care with the Family Support Scale. The LSS-P discriminated, in some aspects, between two-parent visiting the ward for treatment or check-up. The conclusion is that this first version of the LSS-P was valid and reliable (internal consistency) to a certain extent, but that the instrument should be tested on larger samples and during different phases of the disease.

Life situation and problems as reported by children with cancer and their parents.

In recent years, the intensification of treatment for children with cancer has resulted in a considerable increase in the number of those who are cured. The intensive treatment has, however, led to a number of problems for the children and their families. The aim of this study was to identify children's experience of problems related to their cancer and the disease-effect on the child's life situation. Five children with varying diagnoses and treatment plans and five parents were interviewed separately. The qualitative interview data were compared with a quantitative measurement of problems. The interview data were analyzed by two of the authors according to qualitative analysis processes. Six categories regarding influencing factors on the children's life situation were found: (1) medical treatment and side effects, (2) isolation, (3) togetherness and support, (4) being in the center, (5) feelings and reactions, and (6) quality of care. About half of the variables on the list of problems were mentioned in 1 or more of the 10 interviews. Study findings suggest that health care personnel help children with cancer to reduce their fear of painful and frightening procedures by creating a relationship with the child.

Treatment of pain in pediatric oncology: a Swedish nationwide survey.

Pain treatment is a crucial aspect in the care of children with cancer and there are many studies demonstrating inefficient pain treatment. In this study, questionnaires dealing with pain treatment of children with malignant diseases were sent to all (47) pediatric departments in Sweden. The aims of this nationwide survey were to evaluate the extent and causes of pain, the use of methods for pain evaluation (e.g. analysis of type of pain and monitoring of pain intensity), principles of pain management, side effects of pain treatment and the educational needs of physicians and nurses regarding these issues. The response rate was 100%. Answers from physicians and nurses reveal that pain is a common symptom during different periods of cancer treatment. Pain due to treatment and procedures is a greater problem than pain due to the malignant disease itself. Instruments for the measurement of pain intensity and analysis of the type of pain are still rarely used. Most physicians (63%) follow the analgesic 'ladder' principle recommended by World Health Organization (WHO). According to a majority of physicians and nurses (72%), pain could be treated more effectively than it is presently, and 64% state that they need more time for the management of pain. Both physicians and nurses state that they need additional education in different areas of pain evaluation and pain treatment. Swedish treatment practices for the management of pediatric cancer pain roughly follow the published guidelines, but many improvements are still necessary.

Risk of subsequent malignant neoplasms among 1,641 Hodgkin's disease patients diagnosed in childhood and adolescence: a population-based cohort study in the five Nordic countries. Association of the Nordic Cancer Registries and the Nordic Society of Pediatric Hematology and Oncology.

PURPOSE: To assess the risk of subsequent malignant neoplasms among Hodgkin's disease patients diagnosed before 20 years of age in the five Nordic countries (Denmark, Finland, Iceland, Norway, and Sweden). PATIENTS AND METHODS: There were 1,641 Hodgkin's disease patients identified through the national cancer registries since the 1940s or 1950s. The patients were monitored for 17,000 person-years until the end of 1991. Expected figures were derived from the age-specific incidence rates in each country and standardized incidence ratios (SIR) were calculated. RESULTS: A total of 62 subsequent neoplasms were diagnosed (SIR, 7.7; 95% confidence interval [CI], 5.9 to 9.9). The overall cumulative risk of subsequent neoplasms was 1.9% at the 10-year follow-up point, 6.9% at 20 years, and 18% at 30 years. There were 26 subsequent neoplasms among males (SIR, 6.5; 95% CI, 4.3 to 9.6) and 36 among females (SIR, 8.9; 95% CI, 6.2 to 12), of which 16 were breast cancers (SIR, 17; 95% CI, 9.9 to 28). High risks were seen for thyroid cancer (SIR, 33; 95% CI, 15 to 62), for secondary leukemia (SIR, 17; 95% CI, 6.9 to 35), and for non-Hodgkin's lymphoma (SIR, 15; 95% CI, 4.9 to 35). The relative risk increased from 3.3 (95% CI, 1.2 to 7.1) for Hodgkin's disease patients diagnosed in the 1940s and 1950s to 15 (95% CI, 7.4 to 27) in the 1980s. The highest risk of secondary leukemia (SIR, 68; 95% CI, 18 to 174) was seen among those diagnosed with Hodgkin's disease in the 1980s. CONCLUSION: Patients who survive Hodgkin's disease at a young age are at very high relative risk of subsequent malignant neoplasms throughout their lives. In particular, the high relative risk of breast cancer following Hodgkin's disease in the teenage years calls for enhanced activity for early diagnosis.