Effect of vitamin D3 supplementation on Staphylococcus aureus nasal carriage: a randomized, double-blind, placebo-controlled trial in healthy adults.

Observational studies have reported an inverse association between serum 25-hydroxyvitamin D (25OHD) concentrations and Staphylococcus aureus nasal carriage; however, clinical trials of vitamin D supplementation are lacking. To assess the effect of vitamin D3 supplementation on persistent S. aureus nasal carriage we conducted a randomized, double-blind, placebo-controlled trial among 322 healthy adults. Participants were given an oral dose of either 200 000 IU vitamin D3 for each of 2 months, followed by 100 000 IU monthly or placebo in an identical dosing regimen, for a total of 18 months. Nasal swabs for S. aureus culture and serum for 25OHD measurement were obtained at baseline, 6, 12 and 18 months of study. The mean baseline concentration of 25OHD was 72 nM (SD 22 nM). Vitamin D3 supplementation increased 25OHD levels which were maintained at >120 nM throughout the study. Nasal colonization by S. aureus was found in 31% of participants at baseline. Persistent carriage, defined as those that had positive S. aureus nasal cultures for all post-baseline swabs, occurred in 20% of the participants but vitamin D3 supplementation was not associated with a reduction in persistent carriage (OR = 1.39, 95% CI 0.63-3.06). Risk factor analysis showed that only gender was significantly associated with carriage, where women were less likely to be carriers than men (relative risk 0.83, 95% CI 0.54-0.99). Serum 25OHD concentrations were not associated with the risk of carriage. In conclusion, monthly administration of 100 000 IU of vitamin D3 did not reduce persistent S. aureus nasal carriage.

Incidence and characteristics of viral community-acquired pneumonia in adults.

BACKGROUND: In adults, viral causes of community-acquired pneumonia (CAP) are poorly characterised. The aims of this study were to characterise the viral aetiology of CAP in adults by using an extensive array of viral diagnostic tests and to compare the characteristics of viral pneumonia with those of pneumococcal pneumonia. METHODS: Adults admitted to Christchurch Hospital over a 1-year period with CAP were included in the study. Microbiological testing methods included blood and sputum cultures, urinary antigen testing for Streptococcus pneumoniae and Legionella pneumophila, antibody detection in paired sera and detection of respiratory viruses in nasopharyngeal swabs by immunofluorescence, culture and PCR. RESULTS: Of 304 patients with CAP, a viral diagnosis was made in 88 (29%), with rhinoviruses and influenza A being the most common. Two or more pathogens were detected in 49 (16%) patients, 45 of whom had mixed viral and bacterial infections. There were no reliable clinical predictors of viral pneumonia, although several variables were independently associated with some aetiologies. The presence of myalgia was associated with pneumonia caused by any respiratory virus (OR 3.62, 95% CI 1.29 to 10.12) and influenza pneumonia (OR 190.72, 95% CI 3.68 to 9891.91). Mixed rhinovirus/pneumococcal infection was associated with severe disease. CONCLUSIONS: Virus-associated CAP is common in adults. Polymicrobial infections involving bacterial and viral pathogens are frequent and may be associated with severe pneumonia.

A model for the spread and control of pandemic influenza in an isolated geographical region.

In the event of an influenza pandemic, the most probable way in which the virus would be introduced to an isolated geographical area is by an infected traveller. We use a mathematical model, structured on the location at which infection occurs and based on published parameters for influenza, to describe an epidemic in a community of one million people. The model is then modified to reflect a variety of control strategies based on social distancing measures, targeted antiviral treatment and antiviral prophylaxis and home quarantine, and the effectiveness of the strategies is compared. The results suggest that the only single strategy that would be successful in preventing an epidemic (with R0=2.0) is targeted antiviral treatment and prophylaxis, and that closing schools combined with either closing work places or home quarantine would only prevent such an epidemic if these strategies were combined with a modest level of antiviral coverage.

Human metapneumovirus in children with bronchiolitis or pneumonia in New Zealand.

OBJECTIVES: To confirm the presence of human metapneumovirus (hMPV) in New Zealand and establish its prevalence in selected paediatric patient groups. METHODS: Nasopharyngeal swabs were collected in two separate paediatric studies enrolling children clinically diagnosed with either bronchiolitis or pneumonia and tested for hMPV by polymerase chain reaction. RESULTS: Nucleic acid detection tests demonstrated 5.3% of paediatric bronchiolitis cases were positive for hMPV RNA and 2.7% of children admitted with pneumonia tested positive for hMPV RNA. CONCLUSIONS: The presence of hMPV in New Zealand has been confirmed in two selected paediatric patient groups, namely children diagnosed with bronchiolitis and pneumonia. These results indicate that hMPV is associated with a minority of cases of bronchiolitis or pneumonia in this patient group.

Interferon-alpha2a/ribaviran versus interferon-alpha2a alone for the retreatment of hepatitis C patients who relapse after a standard course of interferon.

AIM: To compare the efficacy of a descalating dose of interferon (48 weeks) versus a combination therapy of interferon and ribavirin (24 weeks) in hepatitis C positive subjects who relapsed within six months of cessation of a standard six month course of interferon three million units thrice weekly. METHODS: All 32 subjects had biopsy proven chronic hepatitis C, were PCR positive and had elevated transaminase enzymes at least one and a half times the upper limit of normal. Subjects were randomly assigned to either a descalating dose of interferon-alpha-2a; six million units thrice weekly for 24 weeks followed by 3 MIU 3x for 24 weeks or interferon three million units thrice weekly for 24 weeks plus ribavirin 1,000 mg/day for 12 weeks. A complete virological response was defined as a negative PCR for HCV RNA at 24 weeks after cessation of therapy. RESULTS: Sixteen patients were assigned to each arm and the sustained virological response was 50% for both the interferon and combination therapy arm (pNS). The biochemical response correlated with the virological response; 7/8 virological responders in the interferon alone had normalisation of transaminase 24 weeks post treatment as did 8/8 of those in the combination arm. One patient withdrew from treatment in the descalating interferon group and three required dose reduction. No subjects in the combination arm discontinued therapy but dose reduction was required in three subjects. CONCLUSION: High dose descalating interferon-alpha 2a and a combination of interferon-alpha 2a and ribavirin were effective in achieving a sustained virological response in 50% of subjects who had relapsed after a standard six month course of interferon.

Detection of Legionella DNA in guinea pig peripheral leukocytes, urine and plasma by the polymerase chain reaction.

Legionella DNA has been detected in respiratory tract, serum and urine samples from patients with pneumonia by the polymerase chain reaction. A guinea pig model was used to assess whether Legionella DNA could also be detected in peripheral leukocytes during active infection. Ten guinea pigs were infected intraperitoneally with Legionella pneumophila serogroup 1, and leukocyte, plasma and urine samples were collected immediately before inoculation and on days 1, 3, 7 and 14 thereafter. All samples were tested for Legionella DNA by the polymerase chain reaction. Overall, Legionella DNA was detected in 55% of leukocyte samples, 28% of urine samples and 21% of plasma samples collected after inoculation. The sensitivity of the polymerase chain reaction on leukocytes was highest for samples collected within 3 days of inoculation. Further studies testing leukocyte samples from human Legionella infection are required to confirm these observations.

Chondrosarcoma of bone: an assessment of outcome.

BACKGROUND: The data on 227 patients who had been managed for a chondrosarcoma at one institution were reviewed to determine the nature of the lesions, the predictors of outcome, and whether there were any ways to change the treatment approaches to improve the results. METHODS: The patients were followed for a mean duration of six years (range, three to twenty-five years). The mean age of the patients was forty-seven years (range, nine to eighty-four years). The most prevalent sites of the tumors were the femur (seventy-eight), the pelvis (fifty-one), and the humerus (thirty-nine). The tumors were divided into two groups according to histological grade. Eighty-six tumors (sixteen atypical enchondromas and seventy grade-1 chondrosarcomas) that were locally destructive but were associated with a low likelihood of metastasis were considered to be low-grade. The remaining 141 lesions, which were locally destructive, potentially metastatic, and capable of causing death, were thought to be high-grade. One hundred and three of these 141 lesions were grade 2, and thirty-eight were grade 3 (eighteen of the thirty-eight were grade 3 only, and twenty were both grade 3 and dedifferentiated). Two hundred and twenty-four patients were managed with resection and a limb-sparing procedure; the remaining three patients had an amputation. Postoperative adjuvant radiation was used for fifty-six patients; chemotherapy, for thirty-five; and both radiation and chemotherapy, for nineteen. Flow cytometric patterns were analyzed for 105 patients. RESULTS: The patients who had a high-grade tumor were older than those who had a low-grade tumor (mean age [and standard deviation], 50+/-17.0 years compared with 40+/-15.9 years; p < 0.001). Pathological fracture, metastasis, local recurrence, and death were more prevalent in the group that had a high-grade lesion (p < 0.001). Predictors of metastasis and death in that group of patients included local recurrence, a pelvic location of the tumor, a tumor that was more than 100 cubic centimeters in size, a ploidic abnormality (aneuploidy coupled with a high mean DNA index), a histological grade of 3, and a dedifferentiated type of tumor (p < 0.001). CONCLUSIONS: Although the data are suggestive, with the numbers available for study we could not detect a significant difference in the rates of pulmonary metastasis and death between the patients who had a grade-3 lesion and those who had a grade-3 lesion that was also dedifferentiated. However, the interval between diagnosis and death was 32+/-22.8 months for the patients who had a grade-3 lesion compared with 5+/-3.7 months for those who had a grade-3 lesion that was also dedifferentiated (p < 0.001). Overall, patients who had had a resection with wide margins (margins extending outside the reactive zone) had a longer duration of survival than did those who had had a so-called marginal resection (margins extending outside the tumor but within the reactive zone) or an intralesional resection (margins within the lesion) (p < 0.04). Adjunctive chemotherapy or radiation, or both (which, it must be noted, was used, without a protocol, in a relatively small number of patients), after an intralesional resection, for recurrent disease, or for distant metastasis did not appear to alter the outcome.

Decreasing length of hospital stay in treatment of osteoid osteoma.

Ninety-eight operative procedures were performed for treatment of osteoid osteoma since 1978 at the authors' institution. During these years there was a progressive decrease in the length of hospital stay, decreasing from a mean of 6.8 days between 1978 and 1980 to 2.6 days between 1994 and 1996. Factors that influenced the length of stay after a surgical procedure include patient age, lesion location, choice of procedure, and surgeon. However, the decline in length of stay with time is independent of these factors, and antedates the era of managed care. Increased reliance on more conservative surgical procedures has markedly diminished the length of hospital stay required in the care of these patients.

Percutaneous radiofrequency coagulation of osteoid osteoma compared with operative treatment.

Osteoid osteoma, a benign bone tumor, has traditionally been treated with operative excision. A recently developed method for percutaneous ablation of the tumor has been proposed as an alternative to operative treatment. The relative outcomes of the two approaches to treatment have not previously been compared, to our knowledge. The rates of recurrence and of persistent symptoms were compared in a consecutive series of eighty-seven patients who were managed with operative excision and thirty-eight patients who were managed with percutaneous ablation with radiofrequency. Patients who had a spinal lesion were excluded. The minimum duration of follow-up was two years. There was a recurrence, defined as the need for subsequent intervention, after operative treatment in six (9 per cent) of sixty-eight patients who had been managed for a primary lesion and in two of nineteen who had been managed for a recurrent lesion. The average length of the hospital stay was 4.7 days for the patients who had a primary lesion and 5.1 days for those who had a recurrent lesion. There was a recurrence after percutaneous treatment in four (12 per cent) of thirty-three patients who had been managed for a primary lesion and in none of five who had been managed for a recurrent lesion. The average length of the hospital stay was 0.2 day for these thirty-eight patients. With the numbers available, we could detect no significant difference between the two treatments with regard to the rate of recurrence. The rate of persistent symptoms (that is, symptoms that did not necessitate additional treatment) was greater than the rate of recurrence. According to responses to a questionnaire, eight (30 per cent) of twenty-seven patients had persistent symptoms after operative treatment and six (23 per cent) of twenty-six patients had persistent symptoms after percutaneous treatment with radiofrequency. Two patients had complications after operative excision, necessitating a total of five additional operations. There were no complications associated with the percutaneous method. The results of the present study suggest that percutaneous ablation with radiofrequency is essentially equivalent to operative excision for the treatment of an osteoid osteoma in an extremity. The percutaneous method is preferred for the treatment of extraspinal osteoid osteoma because it generally does not necessitate hospitalization, it has not been associated with complications, and it is associated with a rapid convalescence.

Individualizing management of aggressive fibromatoses.

PURPOSE: To examine prognostic indicators in aggressive fibromatoses that may be used to optimize case-specific management strategy. METHODS AND MATERIALS: One hundred and seven fibromatoses presenting between 1971 and 1992 were analyzed. The following treatment modalities were utilized: (a) surgery alone for 51 tumors; (b) radiation alone for 15 tumors; and (c) radiation and surgery (combined modality) for 41 tumors. Outcome analysis was based on 5-year actuarial local control rates. RESULTS: Control rates among surgery, radiation therapy, and combined modality groups were 69%, 93%, and 72%. Multivariate analysis identified age < 18 years, recurrent disease, positive surgical margins, and treatment with surgery alone as predictors for failure. Patients treated with surgery alone had control rates of 50% (3 of 6) for gross residual, 56% for microscopically positive margins, and 77% for negative margins. Radiation and surgery resulted in rates of 59% for gross residual, 78% for microscopically positive margins, and 100% (6 of 6) for negative margins. For recurrent vs. primary tumors, control was achieved in 48% vs. 77%, 90% vs. 100% (5 of 5), and 67% vs. 79% in the Surgery, Radiation, and Combined modality Groups, respectively. Patients presenting with multiple disease sites tended to have aggressive disease. A radiation dose-control relation to > 60 Gy was seen in patients with unresected or gross residual disease. Of the patients, 23 with disease involving the plantar region had a control rate of 62%, with significantly worse outcomes in children. CONCLUSIONS: These results are consistent with those found in the relevant literature. They support primary resection with negative margins when feasible. Radiation is a highly effective alternative in situations where surgery would result in major functional or cosmetic defects. When negative surgical margins are not achieved in recurrent tumors, radiation is recommended. Perioperative radiation should be considered in other high-risk groups (recurrent disease, positive margins, and plantar tumors in young patients). Doses of 60-65 Gy for gross disease and 50-60 Gy for microscopic residual are recommended. Observation may be considered for primary tumors with disease remaining in situ when they are located such that progression would not cause significant morbidity. Although plantar lesions in children may represent a group at high risk for recurrence or aggressive behavior, the greater potential for radiation-induced morbidity in this group must also temper its use. Given the inconsistent nature and treatment response of this tumor, it is fundamental that treatment recommendations should be made based on the risk:benefit analysis for the individual patient, dependent on tumor characteristics and location, as well as patient characteristics and preferences.

Prognostic factors for local control of sarcomas of the soft tissues managed by radiation and surgery.

During the past decade, local control of primary sarcomas of the extremities by radiation and conservative surgery has supplanted more radical compartmental resections or amputations. Reviews of others and our published data show that the probability of achieving local control is highly dependent on achieving negative surgical margins. Other factors, such as pathological grade and size, histopathology, and concomitant chemotherapy may also affect local control, to a much lesser extent, although these are strongly correlated with the likelihood of distant metastatic disease. Appreciation of the importance of these different prognostic factors has been fundamental to the development of the current rationale for sarcoma management.

Influenza vaccination in 22 developed countries: an update to 1995.

This study expands and updates through 1995 our earlier report on influenza vaccine use in 18 developed countries. Five of the six countries with high levels of vaccine use in 1992 (> or = 130 doses/1000 population) showed little change or slight declines over the subsequent 3 years. The exception was the United States, where a new federal program for vaccination reimbursement for the elderly helped to increase vaccine distribution from 144 to 239 doses/1000 population. The six countries with medium levels of vaccine use in 1992 (76-96 doses/1000 population) increased to > or = 100 doses/1000 population by 1995. Among the six low-use countries in 1992 (< or = 65 doses/1000 population), only Finland showed substantial improvement (96 doses/1000 population) in 1995. Four new countries were added to the study. In Germany, vaccine use increased to 80 doses/1000 population in 1995, but in Ireland it remained at a low level (48 doses/1000 population). In Korea, vaccine use increased from 17 to 95 doses/ 1000 population during the period 1987-1995. In Japan, very high levels of vaccine use (approximately 280 doses/1000 population) in the early 1980s were associated with vaccination programs for school children. However, vaccine use fell precipitously when these programs were discontinued, and only 2 and 8 doses/1000 population were used in 1994 and 1995, respectively. In all 22 countries, higher levels of vaccine use were associated with vaccination reimbursement programs under national or social health insurance and were not correlated with different levels of economic development. Excluding Japan, in 1995 there was still a greater than fourfold difference between the highest and lowest levels of vaccine use among the other 21 countries in the study. Given its well established clinical effectiveness and cost-effectiveness, none of these countries has yet achieved the full benefits of its programs for influenza vaccination.

Prognostic factors and surgical treatment of osseous metastases secondary to renal cell carcinoma.

BACKGROUND: The purpose of this study was to analyze the survival of 38 cases of metastatic renal cell carcinoma with secondary osseous metastases treated at the Orthopaedic Oncology Unit of the Massachusetts General Hospital. The survival was analyzed because it seemed to be considerably longer than any reported previously in the literature. METHODS: Survival was analyzed with respect to age, gender, site of primary tumor, presence of pathologic fracture, disease free interval, initial presentation with metastasis, solitary versus multiple metastases, and axial versus appendicular metastases. RESULTS: Survival for the entire group was 90% at 6 months, 84% at 1 year, 55% at 5 years, and 39% at 10 years. Age, gender, and presence of pathologic fracture had no influence on survival. Presentation without metastases, long disease free interval between nephrectomy and first metastases, appendicular skeletal location, and solitary metastases were all correlated with longer survival. CONCLUSIONS: In the authors' view, patients with the characteristics correlated with longer survival are appropriate candidates for aggressive surgical resection of bone metastasis.

The results of transplantation of intercalary allografts after resection of tumors. A long-term follow-up study.

We reviewed the results of 104 intercalary allograft procedures that had been performed, between April 1974 and August 1992, in 100 patients, usually after resection of a segment of bone because of an osseous neoplasm. The median duration of follow-up was 5.6 years. Retention of the graft and return to essentially normal function were the measures of success and, on that basis, eighty-seven (84 per cent) of the 104 reconstructions were successful. Of the fifteen limbs in which the reconstruction failed, four were salvaged with insertion of a second allograft and three, with use of some other technique. Of the 104 allograft procedures, eight (including two in patients who had a recurrent tumor) were followed by an amputation; thus, the ultimate rate of salvage was 92 per cent for the entire series. Thirty-one grafts failed to unite at one junction with the host or both, within one year after the operation, and this necessitated eighty-one additional operative procedures to achieve a good result. Life-table regression analysis showed that age, gender, anatomical site, and length of the graft were not associated with significant differences in the over-all outcome. Infection (p = 0.0001); fracture (p = 0.002); stage of the lesion (p = 0.007); and use of adjuvant chemotherapy or radiation, or both (p = 0.008), all had an adverse effect on the survival of the allograft. Despite the relatively high rate of non-union that necessitated additional operations, these data indicate that transplantation of allografts for the treatment of intercalary defects has a high rate of success and usually results in a functional limb.

Use of the polymerase chain reaction to detect Legionella DNA in urine and serum samples from patients with pneumonia.

Legionella pneumonia can be difficult to diagnose. Existing laboratory tests for detecting Legionella species lack sensitivity or provide only a retrospective diagnosis. We used the polymerase chain reaction (PCR) with primers that amplify a 104-base pair segment of the coding region of the 5S tRNA gene to detect Legionella DNA in urine and serum samples from patients with pneumonia. Stored urine and serum samples from patients enrolled in two prospective studies of pneumonia were tested. Legionella DNA was detected in urine and/or serum samples from 18 (64%) of 28 patients with legionella pneumonia diagnosed by conventional tests, but it was not detected in urine or serum samples from 24 patients with pneumonia due to other organisms. The sensitivity of PCR improved to 73% if testing was restricted to samples taken within 4 days of the onset of symptoms. Detection of Legionella DNA in urine and serum promises to be a valuable tool for the rapid diagnosis of legionella pneumonia.

Outbreaks of influenza A among elderly hospital inpatients.

AIMS: To describe two outbreaks of influenza A that occurred in wards catering for assessment, treatment and rehabilitation of elderly patients at the Princess Margaret Hospital in Christchurch. METHODS: Infected patients and staff were identified clinically, and influenza subsequently confirmed or supported in some patients by viral antigen detection, culture of throat and nasopharyngeal swabs or serology. RESULTS: Overall, the attack rate of clinical influenza in the two wards affected was 13 of 27 patients (48%) and 15 of 26 patients (58%) respectively. Of all those with influenza, 13 patients (46%) developed lower respiratory tract infection and there were two deaths (7%) at least in part attributed to influenza. Patients in single rooms were not protected from infection. The vaccination rate among all patients was 18%. Immunised patients had a lower attack rate (21%) than those who had not received influenza vaccine that season (40%). The attack rate amongst staff in each ward was 69% and 36% respectively, and the overall staff vaccination rate was 12%. CONCLUSION: These outbreaks illustrate the severe consequences of influenza in an institutional setting.

Long-term results of allograft replacement in the management of bone tumors.

Over the past 24 years, the authors have implanted >870 massive frozen cadaveric allografts mostly for the treatment of defects created by the resection of a bone tumor. Most of the grafts were obtained from the authors' institutional bone bank. The results show that only stage and type of graft affected outcome predictably. Specifically, grafts for a Stage 2 or Stage 3 tumor had a poorer outcome than those for Stages 0 and 1. The results for allograft arthrodeses were considerably poorer than osteoarticular, intercalary, and allograft plus prosthesis. The other major factors in results were complications--recurrence, infection, fracture, and nonunion--with the former 2 having a profound negative effect on outcome. After the first year of susceptibility to infection (10%) and the third year of increased risk of fracture (19%), the grafts become stable, and approximately 75% are retained by patients and are considered to be successful for >20 years after implantation. Osteoarthritis becomes a problem at approximately 6 years for osteoarticular grafts, and so far, 16% of the patients with distal femoral, proximal tibial, or proximal femoral grafts have required total joint replacements. Although the current results are adequate, they are imperfect, and research should be directed at improving the results.