Socioeconomic status predicts functional disability in patients participating in a back pain trial.

PURPOSE: To investigate whether socioeconomic status in patients with back pain participating in a randomised controlled trial was predictive of functional disability (Roland Disability Questionnaire, RDQ). METHOD: Secondary analysis of data (n = 949) from a national primary care trial of physical treatments for back pain (UKBEAM trial) using multilevel modelling. The three indicators were Townsend scores, educational levels and work status. RESULTS: All indicators were significant predictors of outcome after adjusting for baseline variables. As Townsend scores increased (indicating greater deprivation) RDQ scores (functional disability related to back pain) increased. Lower levels of educational attainment were associated with higher RDQ scores. Those 'Not in Work' reported markedly higher levels of RDQ scores which increased over time. There was no evidence that one particular treatment was more suitable for participants of different socioeconomic status. CONCLUSIONS: The findings from this study add to the body of literature which suggests the importance of socioeconomic factors as an influence on health, including resultant disability related to chronic musculoskeletal conditions such as back pain. Work status was particularly dominant in our findings and may suggest that helping patients with back pain back to work where appropriate, is an especially important part of the management process.

Do baseline characteristics predict response to treatment for low back pain? Secondary analysis of the UK BEAM dataset [ISRCTN32683578].

OBJECTIVES: To identify characteristics of randomized controlled trial participants which predict greater benefits from physical treatments for low back pain. If successful, this would allow more appropriate selection of patients for different treatments. METHODS: We did a secondary analysis of the UK Back pain Exercise And Manipulation trial (UK BEAM n = 1334) dataset to identify baseline characteristics predicting response to manipulation, exercise and manipulation followed by exercise (combined treatment). Rather than simply identifying factors associated with overall outcome, we tested for the statistical significance of the interaction between treatment allocation, baseline characteristics and outcome to identify factors that predicted response to treatment. We also did a post-hoc subgroup analysis to present separate results for trial participants with subacute and chronic low back pain to inform future evidence synthesis. RESULTS: Age, work status, age of leaving school, 'pain and disability', 'quality of life' and 'beliefs' at baseline all predicted overall outcome. None of these predicted response to treatment. In those allocated to combined treatment, there was a suggestion that expecting treatment to be helpful might improve outcome at 1 yr. Episode length at study entry did not predict response to treatment. CONCLUSION: Baseline participant characteristics did not predict response to the UK BEAM treatment packages. Using recognized prognostic variables to select patients for different treatment packages, without first demonstrating that these factors affect response to treatment, may be inappropriate. In particular, this analysis suggests that the distinction between subacute and chronic low back pain may not be useful when considering treatment choices.

Patient perceptions of physical therapy within a trial for back pain treatments (UK BEAM) [ISRCTN32683578].

OBJECTIVES: To explore the views of participants in a randomized controlled trial of physical treatments for low back pain about the treatment packages they received in the trial. METHODS: Within a randomized controlled trial that found small to moderate benefits from adding a manipulation package or an exercise programme to general practice care, we elicited participants' views on the treatment using an open question in participant questionnaires. These data were analysed using an adapted framework approach. RESULTS: We received a total of 1259 comments from 1334 participants. Participants randomized to usual general practice care reported dissatisfaction with receiving only 'usual care', which consisted of providing analgesic medication without providing an explanation for their pain. Those randomized to a manipulation package felt the intervention was appropriate to their needs and commonly reported striking benefits. Participants assigned to the exercise programme developed a sense of self-reliance in managing back pain, although some failed to be sufficiently motivated to continue their exercise regimen outside the classes. CONCLUSIONS: This qualitative analysis has found much clearer differences between the groups than the main quantitative analysis. This suggests that some of the added value from being allocated to additional physical treatment for low back pain is not being captured by existing methods of measurement. Improved methods of assessment that consider a wider range of domains may be needed when interpreting the added value of such treatments to individual patients.

The use of pre-conceptional folic acid as an indicator of uptake of a health message amongst white and Bangladeshi women in Tower Hamlets, east London.

BACKGROUND: The benefit of folic acid is a simple health promotion message of proven effectiveness that is particularly pertinent to a young population with a high birth rate. OBJECTIVE: The aim of the present study was to compare the uptake of a folic acid health message in two different ethnic groups. METHODS: Community antenatal teams in Tower Hamlets were asked to recruit women attending for a booking between October 1997 and July 1998 to the study. Tower Hamlets, in east London, is one of the poorest areas in England and Wales, with an ethnically diverse population. A questionnaire enquiring about age, employment, level of education, use of folic acid in their current pregnancy, understanding of the benefits of folic acid and self-described ethnic group was administered verbally immediately before the booking appointment to those women who agreed to participate. RESULTS: Completed questionnaires were received on 249 women. Univariate analysis showed that white women were 5.7 [95% confidence interval (CI) 2.5, 13.2] times more likely to have taken folic acid supplements before conception than Bangladeshi women. Having controlled for the variables, age, school leaving age, social class, parity, planned pregnancy and 'heard of folic acid', ethnic status remained a significant predictor of taking folic acid, with the odds ratio dropping to 5.2 with a 95% CI (1.1, 25.2). CONCLUSION: The Bangladeshi community in the UK have been shown to have poor access to health information sources, which is consistent with the results of this survey, which shows that a simple and important message has not been acted upon equally by white and Bangladeshi women in east London. This survey lends support to the view that resources and innovative forms of health promotion are needed to ensure that ethnic minority groups have adequate access to health promotion messages.

Review of the role of progesterone in the management of postnatal mood disorders.

Postnatal mood disorders (maternity blues, postnatal depression and puerperal psychosis) are cross-cultural symptoms that are commonly seen in primary care by general practitioners and midwives, by gynecologists and obstetricians, and within the psychiatric services. One of several hypotheses for their causation is falling progesterone levels in the postpartum period. Progesterone supplements are therefore currently used in the treatment of postnatal mood disorders, both in primary and secondary health care settings. The evidence for this is reviewed. The MEDLINE and PSYCHLIT databases from 1966 to 1999 were searched. References reporting observational data on progesterone levels around delivery or therapeutic studies using progesterone were retrieved. Additional references were identified by citation tracking from these and direct contact with available authors. Eight papers were identified. Although there is some weak evidence for its role in maternity blues and some theoretical justification for its use, there is no robust primary research to support the use of progesterone in the treatment of postnatal mood disorders. Progesterone is being used to prevent recurrence of postnatal depression but the evidence supporting its efficacy is lacking. Its use in the treatment of postnatal mood disorders cannot be recommended on the basis of current evidence. Randomized controlled trials are needed to decide if it has a role in the treatment and prevention of postnatal mood disorders.

Searching for antiviral drugs for human papillomaviruses.

The human papillomaviruses (HPVs) are ubiquitous human pathogens that cause a wide variety of benign and pre-malignant epithelial tumours. Of the almost 100 different types of HPV that have been characterized to date, approximately two dozen specifically infect genital and oral mucosa. Mucosal HPVs are most frequently sexually transmitted and, with an incidence roughly twice that of herpes simplex virus infection, are considered one of the most common sexually transmitted diseases throughout the world. A subset of genital HPVs, termed 'high-risk' HPVs, is highly associated with the development of genital cancers including cervical carcinoma. The absence of a simple monolayer cell culture system for analysis and propagation of the virus has substantially retarded progress in the development of diagnostic and therapeutic strategies for HPV infection. In spite of these difficulties, great progress has been made in the elucidation of the molecular controls of virus gene expression, replication and pathogenesis. With this knowledge and some important new tools, there is great potential for the development of improved diagnostic and prognostic tests, prophylactic and therapeutic vaccines, and traditional antiviral medicines.

Differences in DNA packaging genes and sensitivity to benzimidazole ribonucleosides between human cytomegalovirus strains AD169 and Towne.

The AD169 strain of human cytomegalovirus was approximately twofold more sensitive to polyhalogenated benzimidazole ribonucleosides than Towne strain. Sequence differences between the two strains have been identified in genes UL51, UL52, UL56, UL77, UL89 and UL104. Because these genes are involved in cleavage and packaging of viral DNA and the benzimidazole ribonucleosides inhibit this process, these sequence differences may be involved in the difference in drug sensitivity.

Evaluation of two time-specific back pain outcome measures.

STUDY DESIGN: Postal questionnaire to individuals with back pain. OBJECTIVE: To assess the acceptability, validity, and reliability of two existing back pain outcome measures, the Roland-Morris Questionnaire and the Von Korff scales, modified to measure the preceding 4 weeks. SUMMARY OF BACKGROUND DATA: The ideal outcome measure for studies of low back pain and disability remains elusive. Most existing measures assess current pain and disability. Measuring these factors over a preceding 4-week period may be more appropriate. METHODS: Individuals with back pain identified in a community survey were asked to complete the modified questionnaires. Validity was assessed by comparison with the Medical Outcome Study Short Form 36 and two general comparator questions on self-reported pain and disability. Repeatability was assessed using retest questionnaires. RESULTS: Completed questionnaires were returned by 95 individuals with chronic back pain. The modified Roland-Morris Questionnaire and Von Korff pain and Von Korff disability scales were completed satisfactorily by 83 (87%), 89 (94%), and 87 (92%) participants, respectively. Mean scores of the modified measures changed significantly and in a predictable manner with increasing ratings of pain and disability. They also correlated with aspects of the Medical Outcome Study Short Form 36 questionnaire. Retest data suggest that these measures are repeatable. The modified Roland-Morris Questionnaire provided adequate analyzable data only if missing values were imputed, and it explained less of the variance in the comparator questions than the modified Von Korff scales. CONCLUSIONS: The modified Von Korff scales were completed easily and appear to be valid and repeatable in this format.

Management of deliberate self harm in general practice: a qualitative study.

BACKGROUND: It has been estimated that the incidence of deliberate self harm (DSH) is at least 10 times that of suicide. Accident and emergency discharge figures also point to an almost doubling of reported cases of DSH in the early 1990s. AIM: To assess general practitioners' (GPs') views on, and educational requirements for, managing patients following an episode of DSH. METHOD: A qualitative study with 14 GPs (seven male and seven female) from two outer-London boroughs, selected in order to provide a maximum variety sample. Interviews took place between February and April 1997, and data were analyzed using the principles of grounded theory. RESULTS: Most GPs felt that all patients presenting with DSH should be assessed by a psychiatrist. They expressed a preference for working with a community psychiatric nurse rather than a counsellor. Suggestions to improve their working relationship with community mental health teams included provision of one centralized point of referral and ease of access to the service in times of crisis. GPs were sceptical of guidelines, emphasizing that they needed joint ownership in writing them, but most importantly that they needed adequate resources to implement them. Specific changes to postgraduate education were suggested, such as individual educational portfolios. CONCLUSION: Improved working relationships between GPs and community mental health teams are needed in order to provide a more efficient and effective service for patients. Lifelong learning needs to be adapted in a style and approach to suit GPs' individual requirements.

Resistance of human cytomegalovirus to benzimidazole ribonucleosides maps to two open reading frames: UL89 and UL56.

2,5,6-Trichloro-1-beta-D-ribofuranosyl benzimidazole (TCRB) is a potent and selective inhibitor of human cytomegalovirus (HCMV) replication. TCRB acts via a novel mechanism involving inhibition of viral DNA processing and packaging. Resistance to the 2-bromo analog (BDCRB) has been mapped to the UL89 open reading frame (ORF), and this gene product was proposed as the viral target of the benzimidazole nucleosides. In this study, we report the independent isolation of virus that is 20- to 30-fold resistant to TCRB (isolate C4) and the characterization of the virus. The six ORFs known to be essential for viral DNA cleavage and packaging (UL51, UL52, UL56, UL77, UL89, and UL104) were sequenced from wild-type HCMV, strain Towne, and from isolate C4. Mutations were identified in UL89 (D344E) and in UL56 (Q204R). The mutation in UL89 was identical to that previously reported for virus resistant to BDCRB, but the mutation in UL56 is novel. Marker transfer analysis demonstrated that each of these mutations individually caused approximately 10-fold resistance to the benzimidazoles and that the combination of both mutations caused approximately 30-fold resistance. The rate and extent of replication of the mutants was the same as for wild-type virus, but the viruses were less sensitive to inhibition of DNA cleavage by TCRB. Mapping of resistance to UL56 supports and extends recent work showing that UL56 codes for a packaging motif binding protein which also has specific nuclease activity (E. Bogner et al., J. Virol. 72:2259-2264, 1998). Resistance which maps to two different genes suggests that their putative proteins interact and/or that either or both have a benzimidazole ribonucleoside binding site. The results also suggest that the gene products of UL89 and UL56 may be antiviral drug targets.

Can postal prompts from general practitioners improve the uptake of breast screening? A randomised controlled trial in one east London general practice.

OBJECTIVE: To determine the effect on the uptake of breast screening of a personalized letter from the general practitioner recommending mammography, sent to coincide with an invitation from the NHS breast screening programme. DESIGN: Randomised control trial with stratification of prognostic variables. SETTING: A group practice in Hackney, east London. SUBJECTS: 473 women invited for breast screening by the City and East London Breast Screening Service. OUTCOME MEASURE: Attendance for mammography. RESULTS: All women in the randomised trial were followed up; 134 of 236 (57%) randomly allocated to receive the prompting letter attended for mammography compared with 120 of 234 (51%) controls This difference was not significant (chi 2 = 1.43, p = 0.23) CONCLUSION: Personal recommendation by a letter prompting attendance for mammography from the general practitioner known best to women due to be screened did not improve uptake of breast screening in this east London practice. Other strategies are needed to increase uptake of mammography in inner cities.

The use of a back class teaching extension exercises in the treatment of acute low back pain in primary care.

BACKGROUND: Back extension exercises are commonly recommended to treat acute low back pain. Evidence of their beneficial effect is, however, weak. OBJECTIVES: We aimed to demonstrate a benefit of teaching back extension exercises in addition to usual GP care for acute low back pain. METHODS: Patients with acute simple low back pain of less than 28 days duration, presenting to a GP, were randomized either to attend a back class or to receive conventional management. Outcome was measured using changes in the Oswestry disability score and visual analogue pain scale (VAS) on six occasions during 1 year and also a VAS and patient assessment of degree of disability during the previous 6 months at 1 year. RESULTS: Seventy-five patients were recruited. The principal outcome measures showed no difference between the two groups. The treatment group reported less chronic disability at 1 year (50% versus 14%, P < 0.007). CONCLUSIONS: A treatment effect has not been demonstrated, but some patients who would otherwise have reported mild pain were pain free after 1 year. This approach to treating back pain has not been shown to be effective. More much larger studies, with more intensive treatment, are required in order to decide whether physical therapy in primary care is beneficial as treatment for acute back pain.

The Cys607-->Tyr change in the UL97 phosphotransferase confers ganciclovir resistance to two human cytomegalovirus strains recovered from two immunocompromised patients.

Two ganciclovir (GCV)-resistant human cytomegalovirus (HCMV) strains recovered from an AIDS patient (strain VR4990) and a heart transplant recipient (strain VR5474) showed a Cys607-->Tyr change in the UL97-encoded phosphotransferase. No amino acid substitutions were observed in the viral DNA polymerase. Marker transfer experiments showed marked reduction in GCV phosphorylation and drug susceptibility of the recombinant HCMV strain VR4990rec2-1-1. These results further extend the region of the carboxy-terminal domain of the UL97 phosphotransferase involved in GCV substrate recognition.

Crisis: what crisis?

There is a large economic cost associated with low back pain. In 1994 its cost to the United Kingdom (UK) was estimated by the UK Clinical Standards Advisory Group report to be nearly pound sterling 6,000 million (ECU 8,350 million) annually. This principally consists of the indirect costs of lost production and disability payments rather than direct health service costs. A re-examination of the assumptions in the report shows that these costs appear to overestimate the economic cost of back pain by an unquantified, but possibly large, amount. This may restrict the benefit of introducing more effective treatments for back pain.

Inhibition of human cytomegalovirus DNA maturation by a benzimidazole ribonucleoside is mediated through the UL89 gene product.

2-Bromo-5,6-dichloro-1-beta-D-ribofuranosyl benzimidazole (BDCRB) is a member of a new class of benzimidazole ribonucleosides which inhibit human cytomegalovirus (HCMV) late in the replication cycle without inhibiting viral DNA synthesis. We show here that polygenomic concatemeric HCMV DNA does not mature to unit genome length in the presence of BDCRB. To discover the locus of action, virus resistant to BDCRB was selected by serial passage in the presence of the compound. Genetic mapping experiments with BDCRB-resistant virus demonstrated that the resistance phenotype mapped to one amino acid (Asp344Glu; low resistance) or two amino acids (Asp344Glu and Ala355Thr; high resistance) within the product of exon 2 of the HCMV U(L)89 open reading frame. The HCMV U(L)89 open reading frame and its homologs are among the most conserved open reading frames in the herpesviruses, and their products have sequence similarities to a known ATP-dependent endonuclease from the double-stranded DNA bacteriophage T4. These findings strongly suggest that BDCRB prevents viral DNA maturation by interacting with a U(L)89 gene product and that the U(L)89 open reading frame may encode an endonucleolytic subunit of the putative HCMV terminase. Further, since mammalian cell DNA replication does not involve a DNA maturation step, compounds which inhibit viral DNA maturation should be selective and safe.