Unintended consequences of policy change to watchful waiting for asymptomatic inguinal hernias

Introduction

In 2009 the Department of Health instructed McKinsey & Company to provide advice on how commissioners might achieve world class National Health Service productivity. Asymptomatic inguinal hernia repair was identified as a potentially cosmetic procedure, with limited clinical benefit. The Birmingham and Solihull primary care trust cluster introduced a policy of watchful waiting for asymptomatic inguinal hernia, which was implemented across the health economy in December 2010. This retrospective cohort study aimed to examine the effect of a change in clinical commissioning policy concerning elective surgical repair of asymptomatic inguinal hernias.

Methods

A total of 1,032 patients undergoing inguinal hernia repair in the 16 months after the policy change were compared with 978 patients in the 16 months before. The main outcome measure was relative proportion of emergency repair in groups before and after the policy change. Multivariate binary logistic regression was used to adjust the main outcome for age, sex and hernia type.

Results

The period after the policy change was associated with 59% higher odds of emergency repair (3.6% vs 5.5%, adjusted odds ratio [OR]: 1.59, 95% confidence interval [CI]: 1.03–2.47). In turn, emergency repair was associated with higher odds of adverse events (4.7% vs 18.5%, adjusted OR: 3.68, 95% CI: 2.04–6.63) and mortality (0.1% vs 5.4%, p<0.001, Fisher’s exact test).

Conclusions

Introduction of a watchful waiting policy for asymptomatic inguinal hernias was associated with a significant increase in need for emergency repair, which was in turn associated with an increased risk of adverse events. Current policies may be placing patients at risk.     

Sympathetic Reinnervation of the Rat Iris in Organ Culture

Reinnervation of sympathetically denervated rat iris by superior cervical ganglion cells has been demonstrated to occur in vitro. Return of [(3)H]norepinephrine uptake by irises incubated in contact with ganglia was associated with the reappearance of nerve fibers containing catecholamines that were demonstrable by fluorescent histochemistry. The reinnervating neurons appeared to follow the same general pattern of innervation seen in the normal iris, but the density of the neural plexus was much greater. Nerve growth factor influenced the rate and extent of innervation of the iris but not of neuronal growth within the ganglion.     

Phenotypic and functional characterization of T-BAM (CD40 ligand)+ T- cell non-Hodgkin's lymphoma

The precise mechanisms regulating T-helper function have been intensively investigated. We and others have recently identified a new T-cell-B-cell-activating molecule called T-BAM that directs B-cell differentiation by interacting with the CD40 molecule on B cells. Using a specific monoclonal antibody against T-BAM (5C8), we have previously shown that T-BAM expressing T cells are predominantly CD4+CD8- and in normal lymphoid tissue have a unique distribution. However, no information has been obtained regarding the phenotype and functional properties of human neoplastic T cells. Therefore, we investigated T- BAM expression immunohistochemically in 87 well-characterized T-cell non-Hodgkin's lymphomas and lymphoid leukemias (LL). We found that 21/81 neoplasms expressed detectable T-BAM and these positive tumors belong almost exclusively to the CD4+CD8- subtype. In addition, to determine whether T-BAM expression could be induced on T-BAM-LL cells, we activated T-BAM-LLs in vitro and showed that T-BAM could be upregulated only in CD4+CD8- tumors. Our studies clearly show that T- BAM is constitutively expressed in a large number of T-cell neoplasms with a relative mature phenotype (CD4+CD8-) and that only CD4+ neoplastic T cells can be induced in vitro to express this molecule. Additional studies are necessary to identify the biologic significance of T-BAM expression and its potential and clinical implications.     

Platelet-derived growth factor in vivo: levels, activity, and rate of clearance

Platelet-derived growth factor (PDGF) is a potent mitogen for many cultured connective tissue cells. It is present in concentrated form within the platelet alpha-granules and is believed to be released during platelet degranulation at sites of vascular injury. We have used a sensitive radioreceptor assay to measure PDGF levels in whole blood serum from normal humans [17.5 +/- 3.1 (SD) ng/mL] and baboons (2.7 +/- 1.2 ng/mL). PDGF was not detected in plasma from either species. In addition, plasma was found to substantially reduce the ability of added purified PDGF to bind to the cell surface PDGF receptor on cultured cells, suggesting that plasma may contain a PDGF-binding protein that would serve to inactivate PDGF released into plasma. Calculations of PDGF concentrations in serum have been corrected for the effects of the binding protein. 125I-PDGF injected intravenously into normal baboons was cleared rapidly from the plasma (t1/2 = two minutes). The rapid clearance of 125I-PDGF did not result from iodination damage, as purified unlabeled PDGF was cleared with comparable kinetics. The rapid clearance of purified and iodinated PDGF did not result from changes in PDGF structure during purification or from removal of PDGF-associated proteins during purification, as PDGF present in freeze-thaw lysates of fresh platelets was cleared equally rapidly. We conclude that release of PDGF at sites of vascular injury would greatly increase the local concentration of PDGF and that PDGF not localized to the site of injury would be rapidly cleared from the circulation.     

The nyctohemeral rhythm of plasma prolactin: effects of ganglionectomy, pinealectomy, constant light, constant darkness or 6-OH-dopamine administration.

In male rats maintained on a 12 h light-dark schedule (6 AM-6 PM), there is a nyctohemeral cycle of plasma prolactin which consists of a nadir at 11:30 AM and an apogee at approximately 11:30 PM. In rats exposed to constant darkness, this rhythm persists for 7 days. Seven days of constant light, however, reverses this diurnal variation such that plasma prolactin levels peak at 11:30 AM and reach a nadir at approximately 11:30 PM. In animals maintained on a 12 h light-dark cycle, ganglionectomy and lateral ventricular injections of 6-OH-dopamine (250 mug) also appear to reverse the diurnal variation of plasma prolactin, whereas a single injection of 6-OH-dopamine (250 mug) into the third ventricle decreases plasma prolactin values at all times intervals but does not alter the diurnal rhythm. Both sites of 6-OH-dopamine administration markedly deplete hypothalamic dopamine and norepinephrine, but injection of 6-OH-dopamine into the lateral ventricle destroys the catecholaminergic terminals in the pineal, whereas injection of 6-OH-dopamine into the third ventricle does not. Pinealectomy slightly increases the early morning values of plasma prolactin, but otherwise has no effect on the diurnal variation of prolactin. Five conclusions appear to be justified: 1) there is a nyctohemeral rhythm of plasma prolactin, which is reversed by constant light; 2) the pineal gland probably plays no role in the diurnal regulation of plasma prolactin secretion; 3) the diurnal rhythm of plasma prolactin is controlled by sympathetic input into the brain via the superior cervical ganglion; 4) a rhythm of plasma prolactin develops in constant light which is the exact opposite of the normal diurnal variation; 5) there appears to be a noradrenergic pathway in the hypothalamus or brainstem which stimulates release of prolactin.