Importance of sustainable local government funding in tackling health inequalities in the UK.

This article looks at how there is evidence that policies that alter our environment are more effective than those that work to change individual behaviour. In order to create change, a more nuanced methodology to allocate local government funding is needed.

Response-guided neoadjuvant sacituzumab govitecan for localized triple-negative breast cancer: results from the NeoSTAR trial.

BACKGROUND: Sacituzumab govitecan (SG), a novel antibody-drug conjugate (ADC) targeting TROP2, is approved for pre-treated metastatic triple-negative breast cancer (mTNBC). We conducted an investigator-initiated clinical trial evaluating neoadjuvant (NA) SG (NCT04230109), and report primary results. PATIENTS AND METHODS: Participants with early-stage TNBC received NA SG for four cycles. The primary objective was to assess pathological complete response (pCR) rate in breast and lymph nodes (ypT0/isN0) to SG. Secondary objectives included overall response rate (ORR), safety, event-free survival (EFS), and predictive biomarkers. A response-guided approach was utilized, and subsequent systemic therapy decisions were at the discretion of the treating physician. RESULTS: From July 2020 to August 2021, 50 participants were enrolled (median age = 48.5 years; 13 clinical stage I disease, 26 stage II, 11 stage III). Forty-nine (98%) completed four cycles of SG. Overall, the pCR rate with SG alone was 30% [n = 15, 95% confidence interval (CI) 18% to 45%]. The ORR per RECIST V1.1 after SG alone was 64% (n = 32/50, 95% CI 77% to 98%). Higher Ki-67 and tumor-infiltrating lymphocytes (TILs) were predictive of pCR to SG (P = 0.007 for Ki-67 and 0.002 for TILs), while baseline TROP2 expression was not (P = 0.440). Common adverse events were nausea (82%), fatigue (76%), alopecia (76%), neutropenia (44%), and rash (48%). With a median follow-up time of 18.9 months (95% CI 16.3-21.9 months), the 2-year EFS for all participants was 95%. Among participants with a pCR with SG (n = 15), the 2-year EFS was 100%. CONCLUSIONS: In the first NA trial with an ADC in localized TNBC, SG demonstrated single-agent efficacy and feasibility of response-guided escalation/de-escalation. Further research on optimal duration of SG as well as NA combination strategies, including immunotherapy, are needed.

Divining responder populations from survival data.

BACKGROUND: Biomarkers that predict treatment response are the foundation of precision medicine in clinical decision-making and have the potential to significantly improve the efficiency of clinical trials. Such biomarkers may be identified before clinical testing but many trials enroll unselected populations. We hypothesized that time-varying treatment effects in unselected trials may result from identifiable responder subpopulations that may have associated biomarkers. MATERIALS AND METHODS: We first simulated scenarios of clinical trials with biomarker populations of varying prevalence and prognostic and predictive associations to illustrate the impact of subgroup-specific effects on overall population estimates. To show a real-world example of time-dependent treatment effects resulting from a prognostic and predictive biomarker, we re-analyzed data from a published clinical trial (RTOG, Radiation Therapy Oncology Group, 9402). We then demonstrated a quantitative framework to fit survival data from clinical trials using statistical models incorporating known estimates of biomarker prevalence and prognostic value to prioritize predictive biomarker hypotheses. RESULTS: Our simulation studies demonstrate how biomarker subgroups that are both predictive and prognostic can manifest as time-dependent treatment effects in overall populations. RTOG 9402 provides a representative example where 1p/19q co-deletion and IDH mutation biomarker-specific effects led to time-varying treatment effects and a considerable deviation from proportional hazards in the overall trial population. Finally, using biomarker data from The Cancer Genome Atlas, we were able to generate statistical models that correctly identified and prioritized a commonly used biomarker through retrospective analysis of published clinical trial data. CONCLUSIONS: Biomarkers that are both predictive and prognostic can result in characteristic changes in survival results. Retrospectively analyzing survival data from clinical trials may highlight potential indications for which an underlying predictive biomarker may be found.

Radial artery bypass graft is a feasible and durable conduit for challenging infrainguinal revascularization: 17 years of Melbourne experience.

OBJECTIVES: The superiority of autogenous venous conduits in infrainguinal bypass surgery is well established. In the absence of suitable leg or arm veins the radial artery can be utilized as an alternative autogenous conduit. In contrast to cardiac surgery, experience with the radial artery as a conduit for infrainguinal bypass surgery is limited. The purpose of this study was to review the outcomes of our radial artery bypasses over the last 17 years. METHODS: All radial artery bypasses performed between 1995 and 2012 were identified from a prospective database. Patency, limb salvage, and survival were calculated using the Kaplan-Meier survival estimate method. RESULTS: Twenty-nine radial artery bypasses were performed in 28 patients. Median follow-up was 55 months (range 1-170). Twelve-month primary, assisted primary, and secondary patency rates were 49%, 62%, and 73% respectively; Both 3-year and 5-year primary, assisted primary, and secondary patency rates were 49%, 56% and 67% respectively. Limb salvage rate was 75% at 1- and 5-year follow-up. Patient survival at 1, 3, and 5 years was 96%, 88%, and 76%. CONCLUSIONS: For patients with need of challenging infrainguinal revascularization without suitable autogenous venous conduit, a radial artery bypass can be performed safely with favorable long-term patency and limb salvage rates.

Description of measles D4-Hamburg outbreak in Hamburg, Germany, December 2008 to June 2009, which disproportionally affected a local Roma community.

From December 2008 to June 2009 a measles outbreak occurred in the Federal State of Hamburg, Germany. The outbreak affected 216 persons and was caused by a new measles strain termed D4-Hamburg which led to consecutive outbreaks between 2009 and 2011 in at least 12 European countries. Here, we describe epidemiological characteristics of the outbreak and evaluate the control measures taken in Hamburg. In one of the seven boroughs of Hamburg a local Roma community comprised more than 50% of the notified cases.We compared in a stratified analysis the age distribution of these cases with cases of fellow citizens who did not belong to the Roma community. The age group of infants (0-11 months) comprised 33% among the non-Roma measles cases, while in the Roma community only 4% belonged to this stratum. In the stratum of 5-17 year-olds only 8% were affected among the non-Roma cases, whereas in the Roma community 50% belonged to this age group. We discuss the influencing factors that might have led to this difference in age distribution between the two groups.

Diabetic retinopathy equity profile in a multi-ethnic, deprived population in Northern England.

PURPOSE: Equity profiles are an established public health tool used to systematically identify and address inequity within health and health services. Our aim was to conduct an equity profile to identify inequity in eye health across Leeds and Bradford. This paper presents results of findings for diabetic retinopathy in Bradford and Airedale. METHODS: A variety of routine health data were included and sub-analysed by measures of equity, including age, sex, ethnicity, and deprivation to identify inequity in eye health and healthcare. The Spearman Rank Correlation Coefficient was used to determine the association between variables. RESULTS: The prevalence of diagnosed diabetes in Bradford and Airedale district is 6.6% compared to 4.3% in nearby Leeds and 5.1% nationally. The age-standardised prevalence of diagnosed diabetic retinopathy within Bradford and Airedale is 2.21% (95% CI 1.54-2.26%), with a disproportionately high prevalence of disease in the Pakistani population and the most deprived parts of the population. There was a poorer uptake of diabetic retinopathy screening in more deprived parts of the district and the proportions with a higher rate of referral to ophthalmology following the screening in Black and Minority Ethnic populations compared with the white population (13.2% vs 6.9%). Uptake of secondary care outpatient appointments is much lower in more deprived populations. CONCLUSION: Inequalities are inherent in diabetic retinopathy prevalence, diagnosis, and treatment. The reasons for these inequities are multi-factorial and further investigation of reasons for poor uptake of services is required. Addressing the inequalities in eye health and healthcare requires cross-organisational collaboration.

Multidisciplinary approach to carotid stenting.

BACKGROUND: Stroke neurologists, vascular surgeons, interventional neuroradiologists and interventional cardiologists have embraced carotid angioplasty and stenting (CAS) because of potential advantages over carotid endarterectomy (CEA). At Austin Health, a multidisciplinary neuro-interventional group was formed to standardise indications and facilitate training. The aims of this study were to describe our organisational model and to determine whether 30-day complications and early outcomes were similar to those of major trials. METHODS: A clinical protocol was developed to ensure optimal management. CAS was performed on patients with high medical risk for CEA, with technically difficult anatomy for CEA, or who were randomised to CAS in a trial. RESULTS: From October 2003 to May 2008, 47 patients (34 male, mean age 71.5) underwent CAS of 50 carotid arteries. Forty-three cases had ipsilateral carotid territory symptoms within the previous 12 months. The main indications for CAS were high risk for CEA (n= 17) and randomised to CAS (n= 21). Interventionists were proctored in 27 cases. The procedural success rate was 94% with two cases abandoned because of anatomical problems and one because of on-table angina. Hypotension requiring vasopressor therapy occurred in 12 cases (24%). The duration of follow up was one to 44 months (mean 6.8 months). The 30-day rate of peri-procedural stroke or death was 6% and the one-year rate of peri-procedural stroke or death or subsequent ipsilateral stroke was 10.6%. Restenosis occurred in 13% (all asymptomatic). CONCLUSION: A multidisciplinary approach is a useful strategy for initiating and sustaining a CAS programme.

Increasing case numbers of adenovirus conjunctivitis in Germany, 2010.

In 2010 (as of 13 October 2010), the number of adenovirus conjunctivitis cases reported to the Robert Koch Institute in Berlin, Germany, has increased by more than 250% compared with same period in the previous two years. An investigation was initiated to identify spatial or temporal clusters, possible sources of infection and potential connections to cases abroad. The analysis did not show a disproportionately affected sex or age group, but many infections were preceded by exposure to ophthalmological facilities, communal facilities or public places.

[Teleconferences for national surveillance of infectious diseases and public health events in Germany. Evaluation after three quarters in 2009]. / Die telefonische infektionsepidemiologische Bund-Länder-Lagekonferenz in Deutschland. Eine Zwischenbilanz nach drei Quartalen 2009.

Public health threats are increasingly triggered by events which span across international, national and state level jurisdictions. Innovative surveillance methods are needed to ensure adequate and timely response to such threats. In January 2009 the Department of Infectious Disease Epidemiology at the Robert Koch Institute (RKI) established a system of weekly telephone conferences with all competent authorities of the German federal states to identify, discuss and respond to infectious disease events in real-time. A regular and structured platform was developed for use between participants from state level public health authorities, the military and the RKI. During the first three quarters, 46 infectious diseases were covered, including mandatory reports of measles and meningococcal meningitis and outbreaks of cowpox, which does not have to be notified in Germany. Results of a targeted evaluation and a consistently high attendance rate both indicate that the teleconference has met additional needs for supplemental information exchange among participants. The telephone conference has proven to be a useful resource for rapid and direct communication, coordination and evaluation of signals for public health events in Germany.

[Vaccinations in early infancy -- results of an epidemiological cross-sectional study in Hamburg]. / Impfungen im frühen Kindesalter - Ergebnisse einer epidemiologischen Querschnittstudie in Hamburg.

BACKGROUND: National recommendations for vaccine policies in Germany were changed in 2001. Following this advice childhood vaccination for nine preventable diseases including measles, mumps, and rubella (MMR) should be completed within the first two years of life. To achieve this it is recommended that plurivalent combination vaccines should be used. As data on current practice is generally rare and not available for the State of Hamburg, a cross-sectional study amongst families from Hamburg with children born during the year 2000 was conducted between April and August 2003. METHODS: A random sample from the resident register was drawn. Structured telephone interviews were conducted. Information on vaccine status and time of vaccination was collected based on individual vaccination documents. RESULTS: 366 families were included in the study. 286 families (78 %) provided information. For 223 families the statements were reliably confirmed. In this group 180 children (80.7 % CI 76 - 86 %) had received at least one dose of MMR vaccine. 112 (50.2 % CI 44 - 57 %) had received two doses. Within the recommended time intervals 49 % had received the first, respectively 46 % had received the second MMR vaccination. A hexavalent contains vaccine containing the other six antigens was used for 138 of the 223 children (62 % CI 55 - 68 %). For 84 of those children (61 %) vaccination was completed with four doses. For 73 children other combinations including single valent vaccines were used. Among those for only 20 children (27.3 %) a completed vaccination status was reached during the recommended time interval. This gap was mainly due to missing hepatitis B vaccinations. The chance for their vaccination to be completed was more than twice as high for children who received the hexavalent combination vaccine compared to the others (RR 2.5; 95 % CI 1.6 - 3.9). DISCUSSION: The results indicate that the recommendations to complete MMR vaccinations earlier are recognised. Nevertheless about half of the children were vaccinated later than recommended. In order to achieve vaccination coverage which will allow to achieve the goal of measles eradication substantial efforts are still required. Due to relatively large rates of incomplete vaccinations for the other antigens activities should focus on a timely completion of the gaps. The potential of combination vaccines to reach this aim is evident.

Conceptional considerations for a German influenza pandemic preparedness plan.

A pandemic appearance of influenza A virus must be expected at any time. The limitations of health preserving and life-saving resources, which will inevitably be reached in the event of a pandemic, will be accompanied by ethical and possibly social conflicts, which can be lessened or resolved only through precautionary planning, clearly specified competencies and transparent decisions within a social consensus. In case of a shortage of vaccines and virostatic agents, decisions will have to be made with regard to the segment of the population that absolutely must be vaccinated. It is currently estimated that a (monovalent) vaccine developed for a new pandemic strain would only suffice for the single vaccination of approximately half of the German population after a year; only 10-14 million vaccine dosages would be available to provide basic immunization and single boosters to personnel required to maintain basic medical care and essential infrastructure after half a year. In the event of local influenza outbreaks, antiviral chemotherapeutic agents could be used to close the gap until a vaccine can become effective. Even if suitable influenza vaccines and virostatic agents are not sufficiently available at the start of a pandemic, it is still possible to at least prevent an outbreak of two of the most feared secondary infections that accompany influenza: pneumococcal pneumonia or meningitis and illnesses resulting from Haemophilus influenzae. Agreement still needs to be reached with manufacturers for guaranteeing the necessary vaccine production or ensuring that they have a sufficient stock to meet the minimum demand for antiviral agents and agents for symptomatic treatment.

Influenza pandemic: preparedness planning in Germany.

The following conceptual framework formed the basis for a common decision made by the health ministers of Germany's 16 federal states to set up an influenza pandemic preparedness plan. The worst case scenario was used, on the basis of the data from the pandemic of 'Spanish flu', in 1918-20. The priority groups for vaccination were assessed, as well as the potentially available antiviral treatments. National policies could be highly improved by a common European view.

[Skelefon framework concept for defence against risks in unusual epidemics: steps by public health offices]. / Rahmenkonzept zur Gefahrenabwehr bei aussergewöhnlichen Seuchengeschehen - Massnahmen des Gesundheitsamtes -

Necessary anti-epidemic measures have to be promulgated or taken immediately in case of a suspected case of pneumonic plague or a viral haemorrhagic fever which can be transmitted from human to human. A live threatening highly contagious infectious disease may occur at any place in Germany. Therefore each health office should have the relevant information on the available infrastructure in Germany concerning treatment and competence centres, diagnostic laboratories, dispatch of samples and patient transportation. They should also be able to give qualified recommendations to physicians and hospitals concerning the necessary measures in such a case. Contacts at risk have to be notified. Based on a risk assessment and the special living conditions of the contact person they should decide if and which further measures have to be initiated, especially in the case of post-exposure prophylaxis, separation and prohibition of work. In general, imported cases of dangerous infectious diseases quickly find the interest of the media, including all the implications resulting from this. A well-organized cooperation with the media and public relations helps to avoid unnecessary irritations and panic.

Dextran reduces embolic signals after carotid endarterectomy.

One hundred fifty patients undergoing carotid endarterectomy were randomly assigned to receive intravenous 10% dextran 40 or placebo. Transcranial Doppler monitoring of the ipsilateral middle cerebral artery 0 to 1 hour postoperatively detected embolic signals in 57% of placebo and 42% of dextran patients, with overall embolic signal counts 46% less for dextran (p = 0.052). Two to 3 hours postoperatively, embolic signals were present in 45% of placebo and 27% of dextran patients, with embolic signal counts 64% less for dextran (p = 0.040). We conclude that dextran reduces embolic signals within 3 hours of CEA.

ACP Best Practice No 163. Wilson's disease: acute and presymptomatic laboratory diagnosis and monitoring.

Wilson's disease, the most common inherited disorder of copper metabolism, is a recessive genetic condition. The clinical presentation of Wilson's disease is very variable. It is characterised by low serum copper and caeruloplasmin concentrations coupled with the pathological accumulation of copper in the tissues. However, there are diagnostic difficulties and these are discussed. The current value of DNA diagnosis, both in gene tracking in families or as applied to de novo cases, is examined. Wilson's disease can be treated successfully but treatment must be life long. Patients are best treated by specialist centres with experience and expertise in the condition.

An outbreak of Salmonella blockley infections following smoked eel consumption in Germany.

In June 1998, an increased number of persons with Salmonella blockley infection were reported from one German state. Because S. blockley is extremely uncommon in Germany, a case-control study was performed in order to find the source. A total of 13 patients met the case definition. Nine of 12 cases and 2 of 21 controls with food consumption histories reported eating smoked eel (OR 28.5; 95% CI 3.9-235.3). The consumed eel came from four different local smokeries, but could be traced back to fish farms in Italy. This outbreak indicates that eel may be a vehicle for salmonella infection and that the smoking process may not eliminate bacterial contamination from raw fish.

Serogroup C meningococcal disease outbreak associated with discotheque attendance during carnival.

In the week following a carnival during 19-24 February 1998, an outbreak of meningococcal disease occurred in a rural German county. The available isolates belonged to phenotype C:2a:P1.2,5 and were clonally related by pulsed-field gel electrophoresis. A case-control study was done to identify risk factors for the outbreak and to define possible vaccination target groups. Five persons aged 13-16 years who fell ill during 24-27 February were included in the study. Four of 5 cases and 10 of 32 controls visited local discotheques (OR = 8.8; P = 0.06). Cases also visited discotheques more frequently than controls (chi2 for trend, P = 0.0002). Multiple discotheques during the carnival may have been predominant locations of transmission in this outbreak. Because this risk factor was limited in time, a mass community vaccination campaign was not initiated.