Outcome Reporting in Spine Surgery: A Review of Historical and Emerging Trends.

The general objectives of spine surgery are to alleviate pain, restore neurologic function, and prevent or treat spinal deformities or instability. The accumulating expanse of outcome measures has allowed us to more objectively quantify these variables and, therefore, gauge the success of treatments, ultimately improving the quality of the delivered health care. It has become increasingly evident that spinal conditions and their accompanying interventions affect all aspects of a patient's life, including their physical, mental, emotional, and social well-being. This underscores the challenge of creating clinically relevant and accurate outcome measures in spine care, and the reason why there is a growing recognition of the importance of subjective measures such as patient-reported outcome measures, that consider a patients' health-related quality of life. Subjective measures provide valuable insights into patient experiences and perceptions of treatment outcomes, whereas objective measures provide a reproducible glimpse into key radiographic and clinical parameters that are associated with a successful outcome. In this narrative review, we provide a detailed analysis of the most common subjective and objective outcome measures employed in spine surgery, with a special focus on their current role as well as the possible future of outcome reporting.

Systematic review of studies generating individual participant data on the efficacy of drugs for treating soil-transmitted helminthiases and the case for data-sharing.

BACKGROUND: Preventive chemotherapy and transmission control (PCT) by mass drug administration is the cornerstone of the World Health Organization (WHO)'s policy to control soil-transmitted helminthiases (STHs) caused by Ascaris lumbricoides (roundworm), Trichuris trichiura (whipworm) and hookworm species (Necator americanus and Ancylostama duodenale) which affect over 1 billion people globally. Despite consensus that drug efficacies should be monitored for signs of decline that could jeopardise the effectiveness of PCT, systematic monitoring and evaluation is seldom implemented. Drug trials mostly report aggregate efficacies in groups of participants, but heterogeneities in design complicate classical meta-analyses of these data. Individual participant data (IPD) permit more detailed analysis of drug efficacies, offering increased sensitivity to identify atypical responses potentially caused by emerging drug resistance. METHODOLOGY: We performed a systematic literature review to identify studies concluding after 2000 that collected IPD suitable for estimating drug efficacy against STH. We included studies that administered a variety of anthelmintics with follow ups less than 60 days after treatment. We estimated the number of IPD and extracted cohort- and study-level meta-data. PRINCIPAL FINDINGS: We estimate that there exist individual data on approximately 35,000 participants from 129 studies conducted in 39 countries, including 34 out of 103 countries where PCT is recommended. We find significant heterogeneity in diagnostic methods, times of outcome assessment, and the reported measure of efficacy. We also quantify cohorts comprising pre-school age children, pregnant women, and co-infected participants, including with HIV. CONCLUSIONS: We argue that establishing a global IPD repository would improve the capacity to monitor and evaluate the efficacy of anthelmintic drugs, respond to changes and safeguard the ongoing effectiveness of PCT. Establishing a fair, transparent data governance policy will be key for the engagement of the global STH community.

Gaussian plume atmospheric modelling and radiation exposure calculations following the cremation of a deceased thyroid cancer patient treated with iodine-131.

Shortly after treatment with 7200 MBq of 131I, a thyroid cancer patient died and was subsequently cremated. Calculations of the atmospheric emissions of 131I from the crematorium flue were performed using a standard atmospheric pollution Gaussian Plume Dispersal model. Estimates of whole-body and thyroid dose of those potentially exposed were made using OLINDA/EXM dosimetry software. Under the meteorological conditions prevalent at the time of the cremation, and depending on the actual release rate of the 131I, the Western Australian legal limit of 3.7 Bqm-3 for atmospheric emissions of 131I may have been exceeded for distances of up to 440 and 1610 m downwind of the crematorium chimney, with the maximum concentration being between 33 and 392 Bqm-3. Assuming 16% of the inhaled 131I was taken up in the thyroid with the balance in the remainder of the body, the radiation dose to maximally exposed individuals was calculated to be approximately 17.7 µSv to the thyroid and 0.04 µSv to the whole-body. Despite the maximum allowable atmospheric 131I concentration of 3.7 Bqm-3 being exceeded, as the number of people immediately downwind of the crematorium flue in the high concentration zones was very low, and considering the relatively high tolerable dose to the thyroid, the radiation dose to people was probably not a problem in this case. The local limit of 1000 MBq of 131I for the cremation of a deceased patient is reasonable, but with adequate precautions could be significantly increased without any harmful effects to people or the environment.

Radiation safety of outpatient 177Lu-octreotate radiopeptide therapy of neuroendocrine tumors.

PURPOSE: To demonstrate the safety of outpatient 7.8 GBq (177)Lu-DOTA-tyr(3)-octreotate radiopeptide therapy of neuroendocrine tumors by measurement of radiation exposures of hospital personnel, carers and members of the public. METHODS: Seventy-six patients with progressive, metastatic neuroendocrine tumors each received four cycles of prescribed activity of 7.8 GBq (177)Lu-octreotate at 8-week intervals, as an outpatient procedure. Cohorts comprising four patients were treated in one room, each patient remaining in hospital until radiation exposure from them was below the release limit of 25 µSv h(-1) at 1 m. On occasion, a single patient was treated in a single room. Radiation exposures of hospital staff and patient carers were monitored by personal dosimeter, and nearby areas monitored with a survey meter. RESULTS: Mean whole-body radiation exposures per therapy day ranged from 8 µSv (physicist) to 33 µSv (nurse), with exposures to personnel, carers and members of the public well within the limits recommended by the International Commission on Radiological Protection. Patients excreted a mean of 46 % of the total administered activity of (177)Lu-octreotate within 4 h of therapy. CONCLUSION: Lutetium-177-octreotate radiopeptide therapy of neuroendocrine tumors can be safely performed as an outpatient treatment.

Outpatient 131I-rituximab radioimmunotherapy for non-Hodgkin lymphoma: a study in safety.

PURPOSE: This study aimed to establish the safety of outpatient 131I-rituximab radioimmunotherapy by measuring the radiation exposure of hospital staff, carers, and members of the public and by estimating the environmental impact of radioactive urinary excretion. METHODS: Two hundred consecutive outpatients treated with 131I-rituximab radioimmunotherapy of non-Hodgkin lymphoma (NHL) with therapeutic activities between 1 and 4.5 GBq (mean, 2.3 GBq; or between 27 and 121 mCi; mean, 62 mCi) predicated on a prescribed whole-body radiation-absorbed dose of 0.75 Gy were studied. Their 279 family members/carers and 432 visitors wore thermoluminescent dosimeter badges for the week during which the patients were confined to their home after treatment. RESULTS: All 200 patients received 131I-rituximab activities according to the prescribed dose of 0.75 Gy to the whole body. From 200 consecutive patients, over the 7 days after therapy, mean radiation exposure of adult carers was 0.49 mSv (range, <0.01 to 3.67 mSv). To other coresiding family members, mean exposure was 0.23 mSv (range, <0.01 to 1.20 mSv), and for visitors sharing badges, the mean exposure was 0.17 mSv (range, <0.01 to 0.73 mSv). Urinary activity excreted over the week after 131I-rituximab therapy was typically less than 25% of the administered activity. CONCLUSIONS: 131I-rituximab radioimmunotherapy for non-Hodgkin lymphoma may be safely administered on an outpatient basis. The median radiation exposure of carers, cohabitants of the patient, and visitors is well within the limits recommended by international guidelines. Local regulatory agency-designated patient release rate limit of less than 25 µSv/h at 1 m was attained within 1 week of therapeutic 131I-rituximab administration.

Management of fear of radiation exposure in carers of outpatients treated with iodine-131.

OBJECTIVE: To characterise potential fear of radiation exposure in a normal population of individuals who have volunteered to care for a radioactive family member or friend after outpatient radioimmunotherapy (RIT) treatment for cancer, and obtain their knowing and willing acceptance of the risk. METHODS: Over 750 carers of 300 patients confined to their homes for 1 week following outpatient iodine-131 rituximab RIT of lymphoma were interviewed by a nuclear medicine physicist according to a multi-visit integrated protocol designed to minimise radiation exposure, define risk and gain informed consent. RESULTS: Median radiation exposure of carers was 0.49 mSv (range 0.01-3.7 mSv) which is below the Western Australian regulatory limit of 5 mSv for consenting adult carers of radioactive patients. After signing a declaration of consent, only 2 carers of 750 abrogated their responsibility and none of those who carried out their duties expressed residual concerns at the end of the exit interview with respect to their radiation exposure. CONCLUSION: Fear of radiation exposure in a normal population may be characterised as a normal emotional response. In the special case of carers of radioactive patients, this fear may be successfully managed by rational, authoritative and empathic explanation to define the risk and gain willing acceptance within the context of domiciliary patient care.

Standard Operating Procedure for Prospective Individualised Dosimetry for ([131])I-rituximab Radioimmunotherapy of Non-Hodgkin's Lymphoma.

Radioimmunotherapy (RIT) is an attractive therapy for non-Hodgkin's lymphoma (NHL) as it allows targeted tumor irradiation which provides a cytotoxic effect significantly greater than that of the immune-mediated effects of a non-radioactive, or 'cold', antibody alone. Anti-CD20 antibodies such as rituximab are ideal for RIT, as not only is it easily iodinated, but the CD20 antigen is found on more than 95% of B-cell NHL. A standard operating procedure (SOP) has been formulated for personalized prospective dosimetry for safe, effective outpatient (131)I-rituximab RIT of NHL. Over five years, experience of treatment of outpatients with (131)I-rituximab was analyzed with respect to critical organ radiation dose in patients and radiation exposure of their carers. This radiation safety methodology has been refined; and offers the potential for safe, practical application to outpatient (131)I-rituximab RIT of lymphoma in general and in developing countries in particular. Given endorsement and sanction of this SOP by local regulatory authorities the personalized dosimetry paradigm will facilitate incorporation of RIT into the routine clinical practice of therapeutic nuclear oncology worldwide.

Structure and inhibition of herpesvirus DNA packaging terminase nuclease domain.

During viral replication, herpesviruses package their DNA into the procapsid by means of the terminase protein complex. In human cytomegalovirus (herpesvirus 5), the terminase is composed of subunits UL89 and UL56. UL89 cleaves the long DNA concatemers into unit-length genomes of appropriate length for encapsidation. We used ESPRIT, a high-throughput screening method, to identify a soluble purifiable fragment of UL89 from a library of 18,432 randomly truncated ul89 DNA constructs. The purified protein was crystallized and its three-dimensional structure was solved. This protein corresponds to the key nuclease domain of the terminase and shows an RNase H/integrase-like fold. We demonstrate that UL89-C has the capacity to process the DNA and that this function is dependent on Mn(2+) ions, two of which are located at the active site pocket. We also show that the nuclease function can be inactivated by raltegravir, a recently approved anti-AIDS drug that targets the HIV integrase.

An efficient two-step synthesis of metal-free phthalocyanines using a Zn(ii) template.

A new family of cationic phthalocyanines containing four guanidinium groups was synthesized in pyridine-HCl at 120 degrees C; under these conditions zinc was removed from both the starting materials and products to reveal a new synthetic route to metal-free phthalocyanines.

Early surgical treatment for collateral ligament rupture of metacarpophalangeal joints of the fingers.

PURPOSE: Thumb metacarpophalangeal (MCP) collateral ligament ruptures are well-known injuries but those occurring in the other fingers seem to be infrequent according to the literature. We undertook this study to evaluate the real incidence of this type of injury and the results of surgical treatment. METHOD: During a 2-year period care was taken to detect all the patients presenting to our emergency unit with a complete rupture of a collateral ligament of a finger and to perform surgery on them as soon as possible. Clinical reassessment was made regularly until maximal recovery and 2 years after surgery. RESULTS: Ten patients with 12 complete MCP collateral ligament rupture of the fingers were seen during this period. Most of the fingers undergoing surgery regained full mobility within 10.7 weeks on average with no residual instability or pain and with no further problems at 2-year follow up evaluation. CONCLUSIONS: Complete ruptures of the MCP collateral ligaments of the fingers are far more frequent than indicated in the literature. Early surgery was found to give highly satisfactory results and may be justified in cases of gross instability of the finger MCP joint.

Attempted and completed suicide in older subjects: results from the WHO/EURO Multicentre Study of Suicidal Behaviour.

OBJECTIVE: The authors present an analysis of findings for the 65 years and over age group from the WHO/EURO Multicentre Study of Suicidal Behaviour (1989-93). METHODS: Multinational data on non-fatal suicidal behaviour is derived from 1518 subjects in 16 European centres. Local district data on suicide were available from 10 of the collaborating centres. RESULTS: Stockholm (Sweden), Pontoise (France) and Oxford (UK) had the highest suicide attempts rates. In most centres, the majority of elderly who attempted suicide were widow(er)s, often living alone, who used predominantly voluntary drug ingestion. Non-fatal suicidal behaviour decreased with increasing age, whereas suicide rates rose. The ratio between fatal and non-fatal behaviours was 1:2, that for males/females almost 1:1. In the years considered, substantial stability in suicide and attempted suicide rates was observed. As their age increased, suicidal subjects displayed only a limited tendency to repeat self-destructive acts. Moreover, there was little correlation between attempted suicide and suicide rates, which carries different clinical implications for non-fatal suicidal behaviour in the elderly compared with younger subjects in the same WHO/EURO study.

The Hermansky-Pudlak syndrome.

The Hermansky-Pudlak syndrome (HPS) associates oculocutaneous albinism with a haemorrhagic diathesis and the accumulation of ceroid-like material in different tissues. HPS is not an uncommon type of albinism as it was diagnosed in 13.5% (8/59) of our autosomal recessive albinos. These eight patients were evaluated ophthalmologically and haematologically. Apart from the symptoms caused by the albinism, accompanying signs vary from ecchymoses to life threatening haemorrhages and death by associated restrictive lung disease. Recognition of this syndrome by the ophthalmologist can be of major importance in this serious and eventually fatal disorder.